- Email: [email protected]
Shear strain in the adventitial layer of the arterial wall facilitates development of vulnerable plaques
Bioscience Hypotheses (2009) 2, 339e342
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/bihy
Shear strain in the adventitial layer of the arterial wall facilitates development of vulnerable plaques T. Idzenga a,*, G. Pasterkamp b, C.L. de Korte a a b
Clinical Physics Laboratory, UMC St Radboud, Nijmegen, The Netherlands Experimental Cardiology Laboratory, UMC Utrecht, The Netherlands
Received 6 May 2009; accepted 14 May 2009
KEYWORDS Vulnerable plaques; Shear strain; Neovascularisation; Elastography
Abstract Myocardial infarction and stroke are two of the leading causes of death and primarily triggered by destabilization of atherosclerotic plaques. Fatty streaks are known to develop at sites in the arterial wall where shear stress is low. These fatty streaks can develop into more advanced plaques that are prone to rupture. Rupture leads to thrombus formation, which may subsequently result in a myocardial infarction or stroke. The relation between shear stress on the inner (endothelial) layer of the arterial wall in relation to plaque development has been studied extensively. However, a causal relation between adventitial shear forces and atherosclerosis development has never been considered. Arterial stiffening increases with age and may facilitate an increase in shear strain in the adventitial layer, an axial shear between artery and surrounding tissue. In the adventitial layer, a large number of inflammatory cells and perivascular structures are present that are subjected to shear strain. Cyclic strain applied to endothelial cells stimulates neovascularisation via different pathways. The conduit arteries in the human body (e.g. coronary and carotid artery) have their own nutrition supply: the vasa vasorum, which is located in the adventitial layer and sprouts into the intimal layer when atherosclerotic plaque develops. Increased plaque neovascularisation makes the plaques more prone to rupture. Therefore we hypothesize that increased shear strain facilitates the development of vulnerable plaques by stimulation of atherosclerotic plaque neovascularisation that sprouts from the adventitial vasa vasorum. Validation of this hypothesis paves the road to the use of adventitial shear strain (measured using a noninvasive ultrasound technique) as risk assessment in plaque. ª 2009 Elsevier Ltd. All rights reserved.
Introduction * Correspondence to: Tim Idzenga, Clinical Physics Laboratory, UMC St Radboud, Route 833, P.O. Box 9101, 6500HB Nijmegen, The Netherlands. Tel.: þ31 24 3668968. E-mail address: [email protected] (T. Idzenga). URL: http://www.elastography.eu
Myocardial infarction and stroke are two leading causes of death [1,2]. The primary trigger for these two causes is destabilization of atherosclerotic plaques. In 76% of the myocardial infarctions and strokes, rupture of plaques with
1756-2392/$ - see front matter ª 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.bihy.2009.05.002
340 superimposed thrombus formation is involved [3]. Although atherosclerosis is a systemic disease, plaques usually develop in the conducting arteries (e.g. the coronary, carotid and femoral artery). They start as so called ‘fatty streaks’ on the intimal layer of the arterial wall and may develop into advanced vulnerable plaques that are prone to rupture. Vulnerable plaques mostly consist of a large pool of lipids and thrombogenic material covered by a thin fibrous cap [4]. When the fibrous cap ruptures, blood comes in contact with the contents of the core leading to thrombus formation, which may cause a heart attack or stroke by blocking a coronary or cerebral artery. Plaques can be detected using different imaging modalities, however detection of the proneness to rupture is challenging. It is however possible to detect plaque properties that are presumed to be related to the occurrence of events. The detection and quantification of these properties requires development of dedicated imaging techniques. The adventitia, media and the atherosclerotic plaques of the coronary and carotid arteries have their own nutrition supply: the vasa vasorum, a network of small microvessels. When atherosclerosis develops, the vasa vasorum increases including plaque neovascularisation, which is thought to play an important role in the progression of atherosclerosis. In the 50s the general assumption was that the lipids found in plaques were filtered from the main bloodstream through the endothelial lining (filtration theory, formalized by Page [5]). It was hypothesized that the lipid content builds up in the plaque, increasing the lipid pool and developing the plaque into a vulnerable plaque. In the 80s, the potential role of the vasa vasorum got more attention. Groszek and Grundy [6] identified three pathways for the contribution of the vasa vasorum to plaque formation: A. Contribution of the leaky vasa vasorum to the influx of lipoprotein. B. Prevention of lipoprotein removal resulting in plaque development. C. Insudation of lipoproteins via the secondary vessels greatly increases the rate of atheroma build up and degeneration of the arterial wall. A fourth identified pathway is that angiogenesis in the fibrous cap weakens the cap and makes the plaque more prone to rupture [7]. There is also evidence that the neovascularisation in the vasa vasorum promotes plaque growth [8]. In patients with acute myocardial infarction the number of microvessels was increased. And in plaques with a fibrous cap the neovessel density was higher in ruptured plaques than in the non-ruptured plaques [9]. The latter study also showed an incremental relation between neovascularisation and inflammation of the plaque. Furthermore, leaky neovessels can lead to haemorrhage in the plaque. Erythrocytes themselves consist for a large amount out of cholesterol and they can thereby accelerate lipid pool formation in the plaque [10]. These results greatly support the possibility of a causal relation between the growth of the vasa vasorum, plaque neovascularisation and plaque development. Question remains however, what stimulates the plaque neovascularisation? There is evidence that cyclic strain increases tubulogenesis by endothelial cells via various pathways [11e15]. The cyclic application of strain triggered the endothelial and smooth muscle cells in the arterial wall to stimulate neovascularisation in the vasa vasorum. Aging of the arteries or stiffening of the arterial wall with
T. Idzenga et al. increasing age could lead to an increased application of cyclic strain. The compliance of the arteries is known to decrease with increasing age, i.e. the arteries get stiffer with aging [16]. When the arterial wall stiffens, shear stress on the endothelium by the pulsating blood flow might increase displacement of the artery with respect to the surrounding tissue. This results in an increase in shear strain in the adventitial layer that might lead to the development of vulnerable plaques. The role of neovascularisation in plaque development and the stimulation of this neovascularisation by application of cyclic strain lead to the following hypothesis:
Hypothesis As a possible factor stimulating atherosclerotic plaque progression we propose that adventitial shear strain induces neovascularisation in all layers of the arterial wall. The pulsating nature and the viscosity of the blood through the arteries induce cyclic shear stress between the blood and the endothelium. With increased arterial stiffness (due to increasing age) this could result in increased shear strain in the adventitial layer. On ultrasound images in vivo it can be observed that during these cyclic luminal shear movements the entire carotid arterial wall moves in an axial direction with respect to the surrounding tissue. Via the ‘pathways’ that have been identified in vitro, this cyclic shear strain could stimulate neovascularisation. Therefore, our hypothesis is that the shear strain induced in the adventitial layer initiates and/or stimulates neovascularisation of the vasa vasorum, which in turn accelerates plaque progression by intraplaque neovascularisation, inflammation and bleeding: these are all determinants of a rupture prone vulnerable plaque.
Evaluation of hypothesis It is known that the shear stress acting on the intima layer, induced by the blood flow, correlates with atherosclerotic plaque formation [17], plaques tend to develop at sites with low shear stress [18]. However, when a plaque has formed at that site the shear stresses induced by the blood flow are increased at the upstream shoulder and decreased at the downstream shoulder of the plaque [18]. Dirksen et al. found a significant difference between the concentrations of smooth muscle cells and macrophages between the up- and down-stream shoulder of a plaque [19]. This indicates a relation between shear stress and plaque instability. However, increased shear stress at the upstream shoulder could also result in an increase in shear strain. If the hypothesis is true this would suggest that increased neovascularisation could be stimulated at the upstream shoulder. This might stimulate the development of an existing plaque into a vulnerable plaque or weaken the upstream shoulder and makes it more prone to rupture. As an example, in the coronary arteries thin-capped fibroatheromas are more frequently observed in the proximal part of the left anterior descending and the left circumflex coronary artery as opposed to the right coronary artery [20]. The amount of stress and strain between arteries and epicard is expected to be the highest in the left ventricle.
Shear strain in the adventitial layer of the arterial wall Plaque ruptures also occur more frequently at these sites [21]. As mentioned previously, another possible cause for increase in shear strain in the adventitial layer might be arterial stiffening due to aging. Stiffening results in an increase in shear strain that might lead to the development of vulnerable plaques. In the case of the hypothesis being valid, assessment of shear strain in the adventitial layer of the carotid artery could possibly predict the likelihood of a plaque to develop into a vulnerable plaque. To make these applications of the hypothesis possible an easily applicable method to measure shear strain should be available as a screening tool. A possible method for measuring these strains is visualization of tissue displacement using noninvasive ultrasound [22,23] with techniques to derive displacement of tissue in the plaque from the sequentially recorded ultrasound frames. Using invasive ultrasound it is only possible to monitor displacement of the carotid arterial wall in radial and circumferential direction as a result of pulsating blood flow. With a conventional linear array transducer, displacement of different layers of the carotid arterial wall can be estimated in the direction of the blood flow. From the lateral displacement of two adjacent layers the shear strain between these layers can be calculated, and thus also the shear strain between adventitial layer of the carotid arterial wall and the surrounding tissue can be estimated. This technique is noninvasive, easily applicable and the acquisition time is short and therefore it can easily be used as a screening tool for the development of vulnerable plaques.
341
[2] [3]
[4]
[5] [6]
[7]
[8] [9]
[10]
Conclusion We pone the hypothesis that shear strain between the adventitial layer of the larger arteries (e.g. coronary and carotid artery) and the surrounding tissue stimulates neovascularisation in the vasa vasorum and consequently promotes vulnerable plaque development. Measurement of this shear strain using a noninvasive ultrasound screening tool could then estimate the likelihood of a plaque to develop into a vulnerable plaque. With such early detection of vulnerable plaques timely treatment can prevent myocardial infarctions and strokes in patients with plaques present in the coronary and/or carotid artery.
Conflict of interest
[11]
[12]
[13]
[14]
[15]
There are no conflicts of interest to report.
Acknowledgement This research was supported by the Technology Foundation STW, an applied division of the Dutch Organisation for Scientific Research (NWO) and the technology programme of the Ministry of Economic Affairs.
[16]
[17] [18]
References [19] [1] Thom T, Haase N, Rosamond W, Howard VJ, Rumsfeld J, Manolio T, et al. Heart disease and stroke statistics e 2006 update: a report from the American Heart Association
Statistics Committee and Stroke Statistics Subcommittee. Circulation 14-2-2006;113:e85e151. Weintraub HS. Identifying the vulnerable patient with rupture-prone plaque. Am J Cardiol 16-6-2008;101:3Fe10F. Kolodgie FD, Burke AP, Skorija KS, Ladich E, Kutys R, Makuria AT, et al. Lipoprotein-associated phospholipase A2 protein expression in the natural progression of human coronary atherosclerosis. Arterioscler Thromb Vasc Biol 2006;26: 2523e9. Schaar JA, Muller JE, Falk E, Virmani R, Fuster V, Serruys PW, et al. Terminology for high-risk and vulnerable coronary artery plaques. Report of a meeting on the vulnerable plaque, June 17 and 18, 2003, Santorini, Greece. Eur Heart J 2004;25: 1077e82. Page IH. Atherosclerosis; an introduction. Circulation 1954;10: 1e27. Groszek E, Grundy SM. The possible role of the arterial microcirculation in the pathogenesis of atherosclerosis. J Chronic Dis 1980;33:679e84. Tureyen K, Vemuganti R, Salamat MS, Dempsey RJ. Increased angiogenesis and angiogenic gene expression in carotid artery plaques from symptomatic stroke patients. Neurosurgery 2006;58:971e7. Isner JM. Cancer and atherosclerosis: the broad mandate of angiogenesis. Circulation 6-4-1999;99:1653e5. Moreno PR, Purushothaman KR, Fuster V, Echeverri D, Truszczynska H, Sharma SK, et al. Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability. Circulation 5-10-2004; 110:2032e8. Arbustini E, Morbini P, D’Armini AM, Repetto A, Minzioni G, Piovella F, et al. Plaque composition in plexogenic and thromboembolic pulmonary hypertension: the critical role of thrombotic material in pultaceous core formation. Heart 2002;88:177e82. Hasaneen NA, Zucker S, Lin RZ, Vaday GG, Panettieri RA, Foda HD. Angiogenesis is induced by airway smooth muscle strain. Am J Physiol Lung Cell Mol Physiol 2007;293:L1059e68. Kou B, Zhang J, Singer DR. Effects of cyclic strain on endothelial cell apoptosis and tubulogenesis are dependent on ROS production via NAD(P)H subunit p22phox. Microvasc Res 27-82008. Morrow D, Cullen JP, Cahill PA, Redmond EM. Cyclic strain regulates the Notch/CBF-1 signaling pathway in endothelial cells: role in angiogenic activity. Arterioscler Thromb Vasc Biol 2007;27:1289e96. Techavipoo U, Chen Q, Varghese T, Zagzebski JA, Madsen EL. Noise reduction using spatial-angular compounding for elastography. IEEE Trans Ultrason Ferroelectr Freq Control 2004; 51:510e20. Von Offenberg SN, Cummins PM, Cotter EJ, Fitzpatrick PA, Birney YA, Redmond EM, et al. Cyclic strain-mediated regulation of vascular endothelial cell migration and tube formation. Biochem Biophys Res Commun 8-4-2005;329: 573e82. Schiffrin EL. Vascular stiffening and arterial compliance. Implications for systolic blood pressure. Am J Hypertens 2004; 17:39Se48S. Cunningham KS, Gotlieb AI. The role of shear stress in the pathogenesis of atherosclerosis. Lab Invest 2005;85:9e23. Slager CJ, Wentzel JJ, Gijsen FJ, Schuurbiers JC, van der Wal AC, van der Steen AF, et al. The role of shear stress in the generation of rupture-prone vulnerable plaques. Nat Clin Pract Cardiovasc Med 2005;2:401e7. Dirksen MT, van der Wal AC, van den Berg FM, van der Loos CM, Becker AE. Distribution of inflammatory cells in atherosclerotic plaques relates to the direction of flow. Circulation 10-11-1998;98:2000e3.
342 [20] Tanaka A, Imanishi T, Kitabata H, Kubo T, Takarada S, Kataiwa H, et al. Distribution and frequency of thin-capped fibroatheromas and ruptured plaques in the entire culprit coronary artery in patients with acute coronary syndrome as determined by optical coherence tomography. Am J Cardiol 15-10-2008;102:975e9. [21] Hong MK, Mintz GS, Lee CW, Lee BK, Yang TH, Kim YH, et al. The site of plaque rupture in native coronary arteries: a threevessel intravascular ultrasound analysis. J Am Coll Cardiol 197-2005;46:261e5.
T. Idzenga et al. [22] Ribbers H, Lopata RG, Holewijn S, Pasterkamp G, Blankensteijn JD, De Korte CL. Noninvasive two-dimensional strain imaging of arteries: validation in phantoms and preliminary experience in carotid arteries in vivo. Ultrasound Med Biol 2007;33:530e40. [23] Hansen H, Lopata R, de Korte C. Non-invasive carotid strain imaging using angular compounding at large beam steered angles: validation in vessel phantoms. IEEE Trans Med Imaging 2009;28(6):872e80.
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/bihy
Shear strain in the adventitial layer of the arterial wall facilitates development of vulnerable plaques T. Idzenga a,*, G. Pasterkamp b, C.L. de Korte a a b
Clinical Physics Laboratory, UMC St Radboud, Nijmegen, The Netherlands Experimental Cardiology Laboratory, UMC Utrecht, The Netherlands
Received 6 May 2009; accepted 14 May 2009
KEYWORDS Vulnerable plaques; Shear strain; Neovascularisation; Elastography
Abstract Myocardial infarction and stroke are two of the leading causes of death and primarily triggered by destabilization of atherosclerotic plaques. Fatty streaks are known to develop at sites in the arterial wall where shear stress is low. These fatty streaks can develop into more advanced plaques that are prone to rupture. Rupture leads to thrombus formation, which may subsequently result in a myocardial infarction or stroke. The relation between shear stress on the inner (endothelial) layer of the arterial wall in relation to plaque development has been studied extensively. However, a causal relation between adventitial shear forces and atherosclerosis development has never been considered. Arterial stiffening increases with age and may facilitate an increase in shear strain in the adventitial layer, an axial shear between artery and surrounding tissue. In the adventitial layer, a large number of inflammatory cells and perivascular structures are present that are subjected to shear strain. Cyclic strain applied to endothelial cells stimulates neovascularisation via different pathways. The conduit arteries in the human body (e.g. coronary and carotid artery) have their own nutrition supply: the vasa vasorum, which is located in the adventitial layer and sprouts into the intimal layer when atherosclerotic plaque develops. Increased plaque neovascularisation makes the plaques more prone to rupture. Therefore we hypothesize that increased shear strain facilitates the development of vulnerable plaques by stimulation of atherosclerotic plaque neovascularisation that sprouts from the adventitial vasa vasorum. Validation of this hypothesis paves the road to the use of adventitial shear strain (measured using a noninvasive ultrasound technique) as risk assessment in plaque. ª 2009 Elsevier Ltd. All rights reserved.
Introduction * Correspondence to: Tim Idzenga, Clinical Physics Laboratory, UMC St Radboud, Route 833, P.O. Box 9101, 6500HB Nijmegen, The Netherlands. Tel.: þ31 24 3668968. E-mail address: [email protected] (T. Idzenga). URL: http://www.elastography.eu
Myocardial infarction and stroke are two leading causes of death [1,2]. The primary trigger for these two causes is destabilization of atherosclerotic plaques. In 76% of the myocardial infarctions and strokes, rupture of plaques with
1756-2392/$ - see front matter ª 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.bihy.2009.05.002
340 superimposed thrombus formation is involved [3]. Although atherosclerosis is a systemic disease, plaques usually develop in the conducting arteries (e.g. the coronary, carotid and femoral artery). They start as so called ‘fatty streaks’ on the intimal layer of the arterial wall and may develop into advanced vulnerable plaques that are prone to rupture. Vulnerable plaques mostly consist of a large pool of lipids and thrombogenic material covered by a thin fibrous cap [4]. When the fibrous cap ruptures, blood comes in contact with the contents of the core leading to thrombus formation, which may cause a heart attack or stroke by blocking a coronary or cerebral artery. Plaques can be detected using different imaging modalities, however detection of the proneness to rupture is challenging. It is however possible to detect plaque properties that are presumed to be related to the occurrence of events. The detection and quantification of these properties requires development of dedicated imaging techniques. The adventitia, media and the atherosclerotic plaques of the coronary and carotid arteries have their own nutrition supply: the vasa vasorum, a network of small microvessels. When atherosclerosis develops, the vasa vasorum increases including plaque neovascularisation, which is thought to play an important role in the progression of atherosclerosis. In the 50s the general assumption was that the lipids found in plaques were filtered from the main bloodstream through the endothelial lining (filtration theory, formalized by Page [5]). It was hypothesized that the lipid content builds up in the plaque, increasing the lipid pool and developing the plaque into a vulnerable plaque. In the 80s, the potential role of the vasa vasorum got more attention. Groszek and Grundy [6] identified three pathways for the contribution of the vasa vasorum to plaque formation: A. Contribution of the leaky vasa vasorum to the influx of lipoprotein. B. Prevention of lipoprotein removal resulting in plaque development. C. Insudation of lipoproteins via the secondary vessels greatly increases the rate of atheroma build up and degeneration of the arterial wall. A fourth identified pathway is that angiogenesis in the fibrous cap weakens the cap and makes the plaque more prone to rupture [7]. There is also evidence that the neovascularisation in the vasa vasorum promotes plaque growth [8]. In patients with acute myocardial infarction the number of microvessels was increased. And in plaques with a fibrous cap the neovessel density was higher in ruptured plaques than in the non-ruptured plaques [9]. The latter study also showed an incremental relation between neovascularisation and inflammation of the plaque. Furthermore, leaky neovessels can lead to haemorrhage in the plaque. Erythrocytes themselves consist for a large amount out of cholesterol and they can thereby accelerate lipid pool formation in the plaque [10]. These results greatly support the possibility of a causal relation between the growth of the vasa vasorum, plaque neovascularisation and plaque development. Question remains however, what stimulates the plaque neovascularisation? There is evidence that cyclic strain increases tubulogenesis by endothelial cells via various pathways [11e15]. The cyclic application of strain triggered the endothelial and smooth muscle cells in the arterial wall to stimulate neovascularisation in the vasa vasorum. Aging of the arteries or stiffening of the arterial wall with
T. Idzenga et al. increasing age could lead to an increased application of cyclic strain. The compliance of the arteries is known to decrease with increasing age, i.e. the arteries get stiffer with aging [16]. When the arterial wall stiffens, shear stress on the endothelium by the pulsating blood flow might increase displacement of the artery with respect to the surrounding tissue. This results in an increase in shear strain in the adventitial layer that might lead to the development of vulnerable plaques. The role of neovascularisation in plaque development and the stimulation of this neovascularisation by application of cyclic strain lead to the following hypothesis:
Hypothesis As a possible factor stimulating atherosclerotic plaque progression we propose that adventitial shear strain induces neovascularisation in all layers of the arterial wall. The pulsating nature and the viscosity of the blood through the arteries induce cyclic shear stress between the blood and the endothelium. With increased arterial stiffness (due to increasing age) this could result in increased shear strain in the adventitial layer. On ultrasound images in vivo it can be observed that during these cyclic luminal shear movements the entire carotid arterial wall moves in an axial direction with respect to the surrounding tissue. Via the ‘pathways’ that have been identified in vitro, this cyclic shear strain could stimulate neovascularisation. Therefore, our hypothesis is that the shear strain induced in the adventitial layer initiates and/or stimulates neovascularisation of the vasa vasorum, which in turn accelerates plaque progression by intraplaque neovascularisation, inflammation and bleeding: these are all determinants of a rupture prone vulnerable plaque.
Evaluation of hypothesis It is known that the shear stress acting on the intima layer, induced by the blood flow, correlates with atherosclerotic plaque formation [17], plaques tend to develop at sites with low shear stress [18]. However, when a plaque has formed at that site the shear stresses induced by the blood flow are increased at the upstream shoulder and decreased at the downstream shoulder of the plaque [18]. Dirksen et al. found a significant difference between the concentrations of smooth muscle cells and macrophages between the up- and down-stream shoulder of a plaque [19]. This indicates a relation between shear stress and plaque instability. However, increased shear stress at the upstream shoulder could also result in an increase in shear strain. If the hypothesis is true this would suggest that increased neovascularisation could be stimulated at the upstream shoulder. This might stimulate the development of an existing plaque into a vulnerable plaque or weaken the upstream shoulder and makes it more prone to rupture. As an example, in the coronary arteries thin-capped fibroatheromas are more frequently observed in the proximal part of the left anterior descending and the left circumflex coronary artery as opposed to the right coronary artery [20]. The amount of stress and strain between arteries and epicard is expected to be the highest in the left ventricle.
Shear strain in the adventitial layer of the arterial wall Plaque ruptures also occur more frequently at these sites [21]. As mentioned previously, another possible cause for increase in shear strain in the adventitial layer might be arterial stiffening due to aging. Stiffening results in an increase in shear strain that might lead to the development of vulnerable plaques. In the case of the hypothesis being valid, assessment of shear strain in the adventitial layer of the carotid artery could possibly predict the likelihood of a plaque to develop into a vulnerable plaque. To make these applications of the hypothesis possible an easily applicable method to measure shear strain should be available as a screening tool. A possible method for measuring these strains is visualization of tissue displacement using noninvasive ultrasound [22,23] with techniques to derive displacement of tissue in the plaque from the sequentially recorded ultrasound frames. Using invasive ultrasound it is only possible to monitor displacement of the carotid arterial wall in radial and circumferential direction as a result of pulsating blood flow. With a conventional linear array transducer, displacement of different layers of the carotid arterial wall can be estimated in the direction of the blood flow. From the lateral displacement of two adjacent layers the shear strain between these layers can be calculated, and thus also the shear strain between adventitial layer of the carotid arterial wall and the surrounding tissue can be estimated. This technique is noninvasive, easily applicable and the acquisition time is short and therefore it can easily be used as a screening tool for the development of vulnerable plaques.
341
[2] [3]
[4]
[5] [6]
[7]
[8] [9]
[10]
Conclusion We pone the hypothesis that shear strain between the adventitial layer of the larger arteries (e.g. coronary and carotid artery) and the surrounding tissue stimulates neovascularisation in the vasa vasorum and consequently promotes vulnerable plaque development. Measurement of this shear strain using a noninvasive ultrasound screening tool could then estimate the likelihood of a plaque to develop into a vulnerable plaque. With such early detection of vulnerable plaques timely treatment can prevent myocardial infarctions and strokes in patients with plaques present in the coronary and/or carotid artery.
Conflict of interest
[11]
[12]
[13]
[14]
[15]
There are no conflicts of interest to report.
Acknowledgement This research was supported by the Technology Foundation STW, an applied division of the Dutch Organisation for Scientific Research (NWO) and the technology programme of the Ministry of Economic Affairs.
[16]
[17] [18]
References [19] [1] Thom T, Haase N, Rosamond W, Howard VJ, Rumsfeld J, Manolio T, et al. Heart disease and stroke statistics e 2006 update: a report from the American Heart Association
Statistics Committee and Stroke Statistics Subcommittee. Circulation 14-2-2006;113:e85e151. Weintraub HS. Identifying the vulnerable patient with rupture-prone plaque. Am J Cardiol 16-6-2008;101:3Fe10F. Kolodgie FD, Burke AP, Skorija KS, Ladich E, Kutys R, Makuria AT, et al. Lipoprotein-associated phospholipase A2 protein expression in the natural progression of human coronary atherosclerosis. Arterioscler Thromb Vasc Biol 2006;26: 2523e9. Schaar JA, Muller JE, Falk E, Virmani R, Fuster V, Serruys PW, et al. Terminology for high-risk and vulnerable coronary artery plaques. Report of a meeting on the vulnerable plaque, June 17 and 18, 2003, Santorini, Greece. Eur Heart J 2004;25: 1077e82. Page IH. Atherosclerosis; an introduction. Circulation 1954;10: 1e27. Groszek E, Grundy SM. The possible role of the arterial microcirculation in the pathogenesis of atherosclerosis. J Chronic Dis 1980;33:679e84. Tureyen K, Vemuganti R, Salamat MS, Dempsey RJ. Increased angiogenesis and angiogenic gene expression in carotid artery plaques from symptomatic stroke patients. Neurosurgery 2006;58:971e7. Isner JM. Cancer and atherosclerosis: the broad mandate of angiogenesis. Circulation 6-4-1999;99:1653e5. Moreno PR, Purushothaman KR, Fuster V, Echeverri D, Truszczynska H, Sharma SK, et al. Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability. Circulation 5-10-2004; 110:2032e8. Arbustini E, Morbini P, D’Armini AM, Repetto A, Minzioni G, Piovella F, et al. Plaque composition in plexogenic and thromboembolic pulmonary hypertension: the critical role of thrombotic material in pultaceous core formation. Heart 2002;88:177e82. Hasaneen NA, Zucker S, Lin RZ, Vaday GG, Panettieri RA, Foda HD. Angiogenesis is induced by airway smooth muscle strain. Am J Physiol Lung Cell Mol Physiol 2007;293:L1059e68. Kou B, Zhang J, Singer DR. Effects of cyclic strain on endothelial cell apoptosis and tubulogenesis are dependent on ROS production via NAD(P)H subunit p22phox. Microvasc Res 27-82008. Morrow D, Cullen JP, Cahill PA, Redmond EM. Cyclic strain regulates the Notch/CBF-1 signaling pathway in endothelial cells: role in angiogenic activity. Arterioscler Thromb Vasc Biol 2007;27:1289e96. Techavipoo U, Chen Q, Varghese T, Zagzebski JA, Madsen EL. Noise reduction using spatial-angular compounding for elastography. IEEE Trans Ultrason Ferroelectr Freq Control 2004; 51:510e20. Von Offenberg SN, Cummins PM, Cotter EJ, Fitzpatrick PA, Birney YA, Redmond EM, et al. Cyclic strain-mediated regulation of vascular endothelial cell migration and tube formation. Biochem Biophys Res Commun 8-4-2005;329: 573e82. Schiffrin EL. Vascular stiffening and arterial compliance. Implications for systolic blood pressure. Am J Hypertens 2004; 17:39Se48S. Cunningham KS, Gotlieb AI. The role of shear stress in the pathogenesis of atherosclerosis. Lab Invest 2005;85:9e23. Slager CJ, Wentzel JJ, Gijsen FJ, Schuurbiers JC, van der Wal AC, van der Steen AF, et al. The role of shear stress in the generation of rupture-prone vulnerable plaques. Nat Clin Pract Cardiovasc Med 2005;2:401e7. Dirksen MT, van der Wal AC, van den Berg FM, van der Loos CM, Becker AE. Distribution of inflammatory cells in atherosclerotic plaques relates to the direction of flow. Circulation 10-11-1998;98:2000e3.
342 [20] Tanaka A, Imanishi T, Kitabata H, Kubo T, Takarada S, Kataiwa H, et al. Distribution and frequency of thin-capped fibroatheromas and ruptured plaques in the entire culprit coronary artery in patients with acute coronary syndrome as determined by optical coherence tomography. Am J Cardiol 15-10-2008;102:975e9. [21] Hong MK, Mintz GS, Lee CW, Lee BK, Yang TH, Kim YH, et al. The site of plaque rupture in native coronary arteries: a threevessel intravascular ultrasound analysis. J Am Coll Cardiol 197-2005;46:261e5.
T. Idzenga et al. [22] Ribbers H, Lopata RG, Holewijn S, Pasterkamp G, Blankensteijn JD, De Korte CL. Noninvasive two-dimensional strain imaging of arteries: validation in phantoms and preliminary experience in carotid arteries in vivo. Ultrasound Med Biol 2007;33:530e40. [23] Hansen H, Lopata R, de Korte C. Non-invasive carotid strain imaging using angular compounding at large beam steered angles: validation in vessel phantoms. IEEE Trans Med Imaging 2009;28(6):872e80.