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Lipoprotein-associated Phospholipase A2, a Marker Linking Inflammation, Atherosclerosis, Vascular Events, Aging, and Cancer
International Journal of Gerontology 9 (2015) 62
Contents lists available at ScienceDirect
International Journal of Gerontology journal homepage: www.ijge-online.com
Editorial
Lipoprotein-associated Phospholipase A2, a Marker Linking Inflammation, Atherosclerosis, Vascular Events, Aging, and Cancer*
Serum lipoprotein-associated phospholipase A2 (Lp-PLA2) is an established predictor of morbidity and mortality for cardiovascular disease and stroke1. Lp-PLA2, also known as platelet-activating factor acetylhydrolase, is an enzyme involved in lipoprotein metabolism and inflammatory responses2,3. It has atherogenic properties and is extensively expressed by advanced atherosclerotic lesions4. In addition to cardiovascular disease, the plasma levels of LpPLA2 have been shown to be significantly increased in elderly patients when compared with the normal population5. Since oxidative stress is implicated in the pathogenesis of atherosclerosis and aging, and phospholipids are particularly sensitive to oxidative stimuli, it is not surprising that elevated levels of Lp-PLA2, a facilitator to hydrolyze the oxidized phospholipids, were observed in both situations. Not only in aging and atherosclerotic lesions, several studies have shown increased plasma levels of Lp-PLA2 in cancer patients6,7. In vivo deletion of the gene expressing Lp-PLA2 (Pla2g7) in mice attenuates intestinal polyposis, suggesting that Lp-PLA2 may play a role in colon tumorigenesis6. Elevated Lp-PLA2 was also demonstrated in patients with aggressive prostate cancer and promoting cancer cell migration and invasion7. Lp-PLA2 is not only a predictive marker for cardiovascular disease and stroke, but also a potential biomarker and putative therapeutic target for certain cancer. These diseases, although diverse clinically, are all implicated by oxidative stress and elevated LpPLA2. Given the increasing research interests on inflammatory tumor microenvironments and cancer metabolism in the pathogenesis of tumor progression, whether Lp-PLA2 also comes in to play with other proinflammatory molecules remains to be determined.
*
References 1. The Lp-PLA2 Studies Collaboration. Lipoprotein-associated phospholipase A2 and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet. 2010;375:1536e1544. 2. Macphee CH, Nelson JJ, Zalewski A. Lipoprotein-associated phospholipase A2 as a target of therapy. Curr Opin Lipidol. 2005;16:442e446. 3. Shi Y, Zhang P, Zhang L, Osman H, et al. Role of lipoprotein-associated phospholipase A2 in leukocyte activation and inflammatory responses. Atherosclerosis. 2007;191:54e62. 4. Caslake MJ, Packard CJ. Lipoprotein-associated phospholipase A2 (platelet-activating factor acetylhydrolase) and cardiovascular disease. Curr Opin Lipidol. 2003;14:347e352. ha V, Bis J, et al. Lipoprotein-associated phospholipase A2 mass 5. Fortunato J, Bla level is increased in elderly subjects with type 2 diabetes mellitus. J Diabetes Res. 2014;2014:1e6. 6. Xu C, Reichert EC, Nakano T, et al. Deficiency of phospholipase A2 group 7 decreases intestinal polyposis and colon tumorigenesis in Apc (Min/þ) mice. Cancer Res. 2013;73:2806e2816. 7. Vainio P, Lehtinen L, Mirtti T, et al. Phospholipase PLA2G7, associated with aggressive prostate cancer, promotes prostate cancer cell migration and invasion and is inhibited by statins. Oncotarget. 2011;2:1176e1190.
Ying-Wen Su* Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan *
Correspondence to: Dr Ying-Wen Su, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan. E-mail address: [email protected]. 28 March 2015 Available online 30 May 2015
Conflict of interest: The author declares no conflict of interest.
http://dx.doi.org/10.1016/j.ijge.2015.05.003 1873-9598/Copyright © 2015, Taiwan Society of Geriatric Emergency & Critical Care Medicine. Published by Elsevier Taiwan LLC. All rights reserved.
Contents lists available at ScienceDirect
International Journal of Gerontology journal homepage: www.ijge-online.com
Editorial
Lipoprotein-associated Phospholipase A2, a Marker Linking Inflammation, Atherosclerosis, Vascular Events, Aging, and Cancer*
Serum lipoprotein-associated phospholipase A2 (Lp-PLA2) is an established predictor of morbidity and mortality for cardiovascular disease and stroke1. Lp-PLA2, also known as platelet-activating factor acetylhydrolase, is an enzyme involved in lipoprotein metabolism and inflammatory responses2,3. It has atherogenic properties and is extensively expressed by advanced atherosclerotic lesions4. In addition to cardiovascular disease, the plasma levels of LpPLA2 have been shown to be significantly increased in elderly patients when compared with the normal population5. Since oxidative stress is implicated in the pathogenesis of atherosclerosis and aging, and phospholipids are particularly sensitive to oxidative stimuli, it is not surprising that elevated levels of Lp-PLA2, a facilitator to hydrolyze the oxidized phospholipids, were observed in both situations. Not only in aging and atherosclerotic lesions, several studies have shown increased plasma levels of Lp-PLA2 in cancer patients6,7. In vivo deletion of the gene expressing Lp-PLA2 (Pla2g7) in mice attenuates intestinal polyposis, suggesting that Lp-PLA2 may play a role in colon tumorigenesis6. Elevated Lp-PLA2 was also demonstrated in patients with aggressive prostate cancer and promoting cancer cell migration and invasion7. Lp-PLA2 is not only a predictive marker for cardiovascular disease and stroke, but also a potential biomarker and putative therapeutic target for certain cancer. These diseases, although diverse clinically, are all implicated by oxidative stress and elevated LpPLA2. Given the increasing research interests on inflammatory tumor microenvironments and cancer metabolism in the pathogenesis of tumor progression, whether Lp-PLA2 also comes in to play with other proinflammatory molecules remains to be determined.
*
References 1. The Lp-PLA2 Studies Collaboration. Lipoprotein-associated phospholipase A2 and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet. 2010;375:1536e1544. 2. Macphee CH, Nelson JJ, Zalewski A. Lipoprotein-associated phospholipase A2 as a target of therapy. Curr Opin Lipidol. 2005;16:442e446. 3. Shi Y, Zhang P, Zhang L, Osman H, et al. Role of lipoprotein-associated phospholipase A2 in leukocyte activation and inflammatory responses. Atherosclerosis. 2007;191:54e62. 4. Caslake MJ, Packard CJ. Lipoprotein-associated phospholipase A2 (platelet-activating factor acetylhydrolase) and cardiovascular disease. Curr Opin Lipidol. 2003;14:347e352. ha V, Bis J, et al. Lipoprotein-associated phospholipase A2 mass 5. Fortunato J, Bla level is increased in elderly subjects with type 2 diabetes mellitus. J Diabetes Res. 2014;2014:1e6. 6. Xu C, Reichert EC, Nakano T, et al. Deficiency of phospholipase A2 group 7 decreases intestinal polyposis and colon tumorigenesis in Apc (Min/þ) mice. Cancer Res. 2013;73:2806e2816. 7. Vainio P, Lehtinen L, Mirtti T, et al. Phospholipase PLA2G7, associated with aggressive prostate cancer, promotes prostate cancer cell migration and invasion and is inhibited by statins. Oncotarget. 2011;2:1176e1190.
Ying-Wen Su* Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan *
Correspondence to: Dr Ying-Wen Su, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan. E-mail address: [email protected]. 28 March 2015 Available online 30 May 2015
Conflict of interest: The author declares no conflict of interest.
http://dx.doi.org/10.1016/j.ijge.2015.05.003 1873-9598/Copyright © 2015, Taiwan Society of Geriatric Emergency & Critical Care Medicine. Published by Elsevier Taiwan LLC. All rights reserved.