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AS-196: Mast Cell Granules Regulated Angiogenesis and Cell Survival in the Myocardial Infarction Rat Model
Wednesday, April 22 - Friday, April 24, 2009 (E-Poster Abstract Zone) (0.4482 ⫾ 0.451 vs 0.5411 ⫾ 0.589, p ⬍0.05) from normal values. (2) The isovolumic relaxation (77.61 ⫾ 16.49 msec vs 64.09 ⫾ 11.82 msec, p ⬍0.05) and isovolumic contraction (28.04 ⫾ 9.57 msec vs 20.45 ⫾ 6.53 msec, p ⬍0.05) times were prolonged and the RVEF (250.02 ⫾ 24.21 msec vs 272.73 ⫾ 20.51 msec, p ⬍0.05) was shortened in patients with ASD compared with control subjects, resulting in a marked increase of the MPI (0.41 ⫾ 0.07 vs 0.31 ⫾ 0.05, p ⬍0.05) from normal values. (3) After transcatheter closure, the RVEDV and RVESV decreased and the RVEF increased markedly; the RV MPI decreased markedly. Conclusion: Transcatheter ASD closure results in rapid normalization of RV volume overload and improvement of RV function.
AS-194 Troponin Elevation: A Prognostic Marker in Patients with Infective Endocarditis. Sharad Jain, Sameer Dani, Jayesh Prajapati, Hasit Joshi, Sunil Thanvi, Kamal Sharma, Anand Shukla, Bhavesh Thakkar, Hitesh Shah, Jay Shah, Tarun Madan, Rutwik Trivedi, Milind Kharche, Vishal Poptani. U.N.Mehta Institute of Cardiology and Research Centre, Ahmedabad, India.
Background: It is well established that hypercholesterolemia can cause endothelial dysfunction. However, in humans, there is lack of data on the relation between high-density lipoprotein (HDL) cholesterol and endothelial dysfunction. Methods: This study consisted of 756 patients (368 men; mean age, 54.7 ⫾ 12.4 years) without significant coronary artery disease who underwent acetylcholine (Ach) provocation testing by injecting incremental doses of 20, 50, and 100 g into the left coronary artery. Significant coronary artery spasm (CAS) was defined as focal or diffuse severe transient luminal narrowing (⬎70%) with or without chest pain or ST-T change on electrocardiography. Results: Conventional risk factors of coronary atherosclerosis, including age, diabetes mellitus, and hypertension are shown (Table). There were statistically significant differences in age, sex, smoking, and HDL level between the 2 groups. However, multiple logistic regression analysis failed to show a significant correlation among smoking, HDL level, and CAS in the 2 groups (p ⫽ 0.775 and p ⫽ 0.393, respectively). TABLE 1
Lipid profile and coronary artery spasm.
Risk Factors, % Background: Elevated troponin (TnI) is increasingly recognized as a marker of cardiac injury and poor outcome in diverse disease states. We hypothesized that patients with infective endocarditis (IE) would have more extensive IE and worse clinical outcomes in positive TnI patients. Methods: TnI was drawn for clinical indications in 26 patients. Patients were divided into 2 groups: the TnI-positive group and the TnI-negative group. Outcomes evaluated were hospital mortality; abscess based on echocardiography or surgery, and central nervous system events. Results: Of 26 patients, 17 patients had TnI values ⬎0.1. There was no difference in age, sex, prosthetic valve IE, prior coronary artery disease, congestive heart failure, or diabetes mellitus between the TnI-positive and TnI-negative groups. Patients with increased TnI were less likely to have isolated right-sided IE, had higher creatinine levels, and were more likely to have a depressed left ventricular ejection fraction. Elevated TnI was associated with the composite of death, abscesses, and cerebrovascular events (p ⬍0-001).When restricted to patients with creatinine £ 1.3 mg/dL (n ⫽ 16), the association between TnI and the composite outcome remained significant (p ⬍0.001) (Table).
Mean age (yrs) Male Mean Creatinine (mg/dl) Hospital Death Abscesses CNS event
TnI Positive
TnI Negative
47.8 12 (72%) 1.8 6 (39%) 5 (33%) 7 (45%)
46 5 (55.6%) 1.1 0 0 1 (5%)
Conclusion: Data demonstrate a strong association of TnI with the composite end point of cerebrovascular events, abscess, or deaths in patients with IE. Further prospective evaluation is needed to fully define the role of TnI in IE.
AS-195 Role of High-Density Lipoprotein and Coronary Artery Endothelial Dysfunction. seung woon Rha, soon young Suh, kanhaiya lal Poddar, kang yin Chen, yong jian Li, zhe Jin, yoshiyasu Minami, jae hyoung Park, cheol ung Choi, jin oh Na, ong euy Lim, jin won Kim, eung ju Kim, chang gyu Park, hong seog Seo, dong joo Oh. Korea University Guro Hospital, Seoul, Republic of Korea.
Age (year) Sex (male, %) Hypertension DM Smoking Cholesterol TG HDL LDL
Provocation (ⴙ) (N ⴝ 423)
Provocation (ⴚ) (N ⴝ 333)
P-Value
56.6 ⫾ 11.5 230 (54.4%) 147 (34.8%) 38 (9.3%) 123 (26.1%) 173.6 ⫾ 36.2 129.8 ⫾ 81.5 50.8 ⫾ 13.2 116.0 ⫾ 70.6
52.2 ⫾ 13.1 138 (41.4%) 107 (32.1%) 27 (8.2%) 66 (20.6%) 176.5 ⫾ 42.0 126.5 ⫾ 85.0 54.1 ⫾ 22.8 112.6 ⫾ 31.6
0.001 0.001 0.449 0.760 0.011 0.34 0.64 0.04 0.57
Conclusion: The lipid profile, including HDL, does not appear to be an independent risk factor for significant CAS. Only age and sex were associated with significant CAS (RR ⫽ 1.03 and 1.77, respectively).
AS-196 Mast Cell Granules Regulated Angiogenesis and Cell Survival in the Myocardial Infarction Rat Model. Jin Sook Kwon, Ae Shin Cho, Sun Mi Shin, Yong Sook Kim, Moon Hwa Hong, Kye Hun Kim, Young Joon Hong, Hyung Wook Park, Ju Han Kim, Myung Ho Jeong, Jeong Gwan Cho, Jong Chun Park, Jung Chaee Kang, Youngkeun Ahn. Chonnam National University Hospital, Gwangju, Republic of Korea. Background: Mast cells are multifunctional cells containing various mediators, such as cytokines, proteases, and histamine. A recent study demonstrated that mast cells have various effects on the progression of disease after acute myocardial infarction (MI). In this study, the effects of mast cell granules (MCGs) at different concentrations on various cell types, such as rat neonatal cardiomyocytes (rCMs), human endothelial progenitor cells (hEPCs), and human umbilical vein endothelial cells (hUVECs), in the rat MI model were evaluated. Methods: To evaluate the effects of MCGs using an in vitro assay, we treated MCGs (concentrations of 1%, 0.1%, 0.01%, and 0.001% of the original dose [2 ⫻ 105 cells/mL]) for 4 or 24 hours in rCMs, hEPCs, and hUVECs in vivo assay, and injected MCGs [2 or 20 mL] into an infarcted rat heart. We analyzed cell survival, cell signals, angiogenesis, and the preservation of left ventricular (LV) function. Results: MCGs increased capillary tube formation and migration of hEPCs, hUVECs and phosphorylation of Akt, ERK in rCMs. Also, in the rat MI model, both 2- and 20- mL MCG treatment increased capillary density 3 times more than in the control rats in the infarct area
The American Journal of Cardiology姞 APRIL 22–24 2009 ANGIOPLASTY SUMMIT ABSTRACTS/E-Poster 83B
EP O S T E R A B S T R A C T S
Wednesday, April 22 - Friday, April 24, 2009 (E-Poster Abstract Zone) (p ⬍0.05 in each). Improvement of LV function was observed in the 2-mL MCG treatment group (p ⬍0.05). Conclusion: The use of the role of MCGs in the regulation of angiogenesis and cell survival could result in improved LV function after MI.
AS-197 WITHDRAWN
AS-198 Oxytocin Accelerates Transmigration of Umbilical Cord Blood– Derived Mesenchymal Stem Cells via Matrix Metalloproteinase– 2 and Matrix Metalloproteinase–9. Yong Sook Kim, Moon Hwa Hong, Jin Sook Kwon, Ae Sin Jo, Sun Mi Shin, Myung Ho Jeong, Jeong Gwan Cho, Jong Chun Park, Jung Chaee Kang, Youngkeun Ahn. Chonnam National University Hospital, Gwangju, Republic of Korea. Background: Oxytocin (OT), a cardiac hormone, is reported as the cardiomyogenic factor for embryonic stem cells. It also stimulates the differentiation of cardiac progenitor cells to cardiomyocytes. We found that the OT receptor (OTR) was highly expressed in umbilical cord blood (USB)–mesenchymal stem cells (MSCs) compared with bone marrow (BM)–MSCs. We designed this study to elucidate whether OT plays an important role in UCB-MSC cellular events. Methods: MSCs were isolated and cultured from UCB and BM. MSCs were treated with OT (100 nmol/L). Angiogenic potential was
evaluated by tube formation, and cell migration was assessed by wound healing assay. The transwell migration activity was determined by using a modified Boyden chamber assay. The expressions of OTR, vWF, angiopoietin (Ang)-1, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9 were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) or Western blot analysis. To assay the enzymatic activities of MMP-2 and MMP-9, MSCs cultured media were analyzed by zymography. Results: The expression level of OTR was higher in UCB-MSCs than BM-MSCs. The proliferation rate of UCB-MSCs was not changed during treatment with OT (0, 10, 100, 1,000 nmol/L). Tube formation was attenuated by OT, and the cell migration rate was not changed by OT treatment. On the other hand, transmigration activity was drastically accelerated by OT treatment. To examine whether MMP expression was induced by OT, the messenger RNA (mRNA) level of MMP-2 and MMP-9 was determined by RT-PCR. OT increased the MMP-2 mRNA in proportion to OT concentration (10, 100, 1,000 nmol/L) in 1 hour. MMP-9 mRNA, not expressed in UCB-MSCs, was increased by 100 nmol/L and 1,000 nmol/L OT treatment in 1 hour and was prolonged to 24 hours. To examine whether MMP-2 and MMP-9 activity was increased by OT, the UCB-MSCs were cultured for 24 hours in the presence or absence of OT (100 nmol/L), and cultured media was analyzed by zymography. Both MMP-2 and MMP-9 activities were increased by OT treatment. Conclusion: OT accelerated the transmigration activity of UCBMSCs, and OT could be used to improve the efficient targeting of UCM-MSCs to injured heart tissue.
EP O S T E R A B S T R A C T S 84B The American Journal of Cardiology姞 APRIL 22–24 2009 ANGIOPLASTY SUMMIT ABSTRACTS/E-Poster
AS-194 Troponin Elevation: A Prognostic Marker in Patients with Infective Endocarditis. Sharad Jain, Sameer Dani, Jayesh Prajapati, Hasit Joshi, Sunil Thanvi, Kamal Sharma, Anand Shukla, Bhavesh Thakkar, Hitesh Shah, Jay Shah, Tarun Madan, Rutwik Trivedi, Milind Kharche, Vishal Poptani. U.N.Mehta Institute of Cardiology and Research Centre, Ahmedabad, India.
Background: It is well established that hypercholesterolemia can cause endothelial dysfunction. However, in humans, there is lack of data on the relation between high-density lipoprotein (HDL) cholesterol and endothelial dysfunction. Methods: This study consisted of 756 patients (368 men; mean age, 54.7 ⫾ 12.4 years) without significant coronary artery disease who underwent acetylcholine (Ach) provocation testing by injecting incremental doses of 20, 50, and 100 g into the left coronary artery. Significant coronary artery spasm (CAS) was defined as focal or diffuse severe transient luminal narrowing (⬎70%) with or without chest pain or ST-T change on electrocardiography. Results: Conventional risk factors of coronary atherosclerosis, including age, diabetes mellitus, and hypertension are shown (Table). There were statistically significant differences in age, sex, smoking, and HDL level between the 2 groups. However, multiple logistic regression analysis failed to show a significant correlation among smoking, HDL level, and CAS in the 2 groups (p ⫽ 0.775 and p ⫽ 0.393, respectively). TABLE 1
Lipid profile and coronary artery spasm.
Risk Factors, % Background: Elevated troponin (TnI) is increasingly recognized as a marker of cardiac injury and poor outcome in diverse disease states. We hypothesized that patients with infective endocarditis (IE) would have more extensive IE and worse clinical outcomes in positive TnI patients. Methods: TnI was drawn for clinical indications in 26 patients. Patients were divided into 2 groups: the TnI-positive group and the TnI-negative group. Outcomes evaluated were hospital mortality; abscess based on echocardiography or surgery, and central nervous system events. Results: Of 26 patients, 17 patients had TnI values ⬎0.1. There was no difference in age, sex, prosthetic valve IE, prior coronary artery disease, congestive heart failure, or diabetes mellitus between the TnI-positive and TnI-negative groups. Patients with increased TnI were less likely to have isolated right-sided IE, had higher creatinine levels, and were more likely to have a depressed left ventricular ejection fraction. Elevated TnI was associated with the composite of death, abscesses, and cerebrovascular events (p ⬍0-001).When restricted to patients with creatinine £ 1.3 mg/dL (n ⫽ 16), the association between TnI and the composite outcome remained significant (p ⬍0.001) (Table).
Mean age (yrs) Male Mean Creatinine (mg/dl) Hospital Death Abscesses CNS event
TnI Positive
TnI Negative
47.8 12 (72%) 1.8 6 (39%) 5 (33%) 7 (45%)
46 5 (55.6%) 1.1 0 0 1 (5%)
Conclusion: Data demonstrate a strong association of TnI with the composite end point of cerebrovascular events, abscess, or deaths in patients with IE. Further prospective evaluation is needed to fully define the role of TnI in IE.
AS-195 Role of High-Density Lipoprotein and Coronary Artery Endothelial Dysfunction. seung woon Rha, soon young Suh, kanhaiya lal Poddar, kang yin Chen, yong jian Li, zhe Jin, yoshiyasu Minami, jae hyoung Park, cheol ung Choi, jin oh Na, ong euy Lim, jin won Kim, eung ju Kim, chang gyu Park, hong seog Seo, dong joo Oh. Korea University Guro Hospital, Seoul, Republic of Korea.
Age (year) Sex (male, %) Hypertension DM Smoking Cholesterol TG HDL LDL
Provocation (ⴙ) (N ⴝ 423)
Provocation (ⴚ) (N ⴝ 333)
P-Value
56.6 ⫾ 11.5 230 (54.4%) 147 (34.8%) 38 (9.3%) 123 (26.1%) 173.6 ⫾ 36.2 129.8 ⫾ 81.5 50.8 ⫾ 13.2 116.0 ⫾ 70.6
52.2 ⫾ 13.1 138 (41.4%) 107 (32.1%) 27 (8.2%) 66 (20.6%) 176.5 ⫾ 42.0 126.5 ⫾ 85.0 54.1 ⫾ 22.8 112.6 ⫾ 31.6
0.001 0.001 0.449 0.760 0.011 0.34 0.64 0.04 0.57
Conclusion: The lipid profile, including HDL, does not appear to be an independent risk factor for significant CAS. Only age and sex were associated with significant CAS (RR ⫽ 1.03 and 1.77, respectively).
AS-196 Mast Cell Granules Regulated Angiogenesis and Cell Survival in the Myocardial Infarction Rat Model. Jin Sook Kwon, Ae Shin Cho, Sun Mi Shin, Yong Sook Kim, Moon Hwa Hong, Kye Hun Kim, Young Joon Hong, Hyung Wook Park, Ju Han Kim, Myung Ho Jeong, Jeong Gwan Cho, Jong Chun Park, Jung Chaee Kang, Youngkeun Ahn. Chonnam National University Hospital, Gwangju, Republic of Korea. Background: Mast cells are multifunctional cells containing various mediators, such as cytokines, proteases, and histamine. A recent study demonstrated that mast cells have various effects on the progression of disease after acute myocardial infarction (MI). In this study, the effects of mast cell granules (MCGs) at different concentrations on various cell types, such as rat neonatal cardiomyocytes (rCMs), human endothelial progenitor cells (hEPCs), and human umbilical vein endothelial cells (hUVECs), in the rat MI model were evaluated. Methods: To evaluate the effects of MCGs using an in vitro assay, we treated MCGs (concentrations of 1%, 0.1%, 0.01%, and 0.001% of the original dose [2 ⫻ 105 cells/mL]) for 4 or 24 hours in rCMs, hEPCs, and hUVECs in vivo assay, and injected MCGs [2 or 20 mL] into an infarcted rat heart. We analyzed cell survival, cell signals, angiogenesis, and the preservation of left ventricular (LV) function. Results: MCGs increased capillary tube formation and migration of hEPCs, hUVECs and phosphorylation of Akt, ERK in rCMs. Also, in the rat MI model, both 2- and 20- mL MCG treatment increased capillary density 3 times more than in the control rats in the infarct area
The American Journal of Cardiology姞 APRIL 22–24 2009 ANGIOPLASTY SUMMIT ABSTRACTS/E-Poster 83B
EP O S T E R A B S T R A C T S
Wednesday, April 22 - Friday, April 24, 2009 (E-Poster Abstract Zone) (p ⬍0.05 in each). Improvement of LV function was observed in the 2-mL MCG treatment group (p ⬍0.05). Conclusion: The use of the role of MCGs in the regulation of angiogenesis and cell survival could result in improved LV function after MI.
AS-197 WITHDRAWN
AS-198 Oxytocin Accelerates Transmigration of Umbilical Cord Blood– Derived Mesenchymal Stem Cells via Matrix Metalloproteinase– 2 and Matrix Metalloproteinase–9. Yong Sook Kim, Moon Hwa Hong, Jin Sook Kwon, Ae Sin Jo, Sun Mi Shin, Myung Ho Jeong, Jeong Gwan Cho, Jong Chun Park, Jung Chaee Kang, Youngkeun Ahn. Chonnam National University Hospital, Gwangju, Republic of Korea. Background: Oxytocin (OT), a cardiac hormone, is reported as the cardiomyogenic factor for embryonic stem cells. It also stimulates the differentiation of cardiac progenitor cells to cardiomyocytes. We found that the OT receptor (OTR) was highly expressed in umbilical cord blood (USB)–mesenchymal stem cells (MSCs) compared with bone marrow (BM)–MSCs. We designed this study to elucidate whether OT plays an important role in UCB-MSC cellular events. Methods: MSCs were isolated and cultured from UCB and BM. MSCs were treated with OT (100 nmol/L). Angiogenic potential was
evaluated by tube formation, and cell migration was assessed by wound healing assay. The transwell migration activity was determined by using a modified Boyden chamber assay. The expressions of OTR, vWF, angiopoietin (Ang)-1, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9 were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) or Western blot analysis. To assay the enzymatic activities of MMP-2 and MMP-9, MSCs cultured media were analyzed by zymography. Results: The expression level of OTR was higher in UCB-MSCs than BM-MSCs. The proliferation rate of UCB-MSCs was not changed during treatment with OT (0, 10, 100, 1,000 nmol/L). Tube formation was attenuated by OT, and the cell migration rate was not changed by OT treatment. On the other hand, transmigration activity was drastically accelerated by OT treatment. To examine whether MMP expression was induced by OT, the messenger RNA (mRNA) level of MMP-2 and MMP-9 was determined by RT-PCR. OT increased the MMP-2 mRNA in proportion to OT concentration (10, 100, 1,000 nmol/L) in 1 hour. MMP-9 mRNA, not expressed in UCB-MSCs, was increased by 100 nmol/L and 1,000 nmol/L OT treatment in 1 hour and was prolonged to 24 hours. To examine whether MMP-2 and MMP-9 activity was increased by OT, the UCB-MSCs were cultured for 24 hours in the presence or absence of OT (100 nmol/L), and cultured media was analyzed by zymography. Both MMP-2 and MMP-9 activities were increased by OT treatment. Conclusion: OT accelerated the transmigration activity of UCBMSCs, and OT could be used to improve the efficient targeting of UCM-MSCs to injured heart tissue.
EP O S T E R A B S T R A C T S 84B The American Journal of Cardiology姞 APRIL 22–24 2009 ANGIOPLASTY SUMMIT ABSTRACTS/E-Poster