Serum from Patients with Severe Alcoholic Liver Cirrhosis Inhibits Proliferation and Migration of Human Coronary Artery Smooth Muscle Cells

Liver cirrhosis has been associated with an increased risk of coronary artery disease and clinical complications following percutaneous coronary revascularization. The present study is based on the hypothesis that cirrhosis may influence intimal hyperplasia following PCI. Sera from 10 patients with alcoholic liver cirrhosis and 10 age-matched healthy controls were used to stimulate cultured human coronary artery smooth muscle cells (HCASMC) for 48 h. HCASMC proliferation, migration, gene expression and apoptosis were investigated. Serum concentrations of growth factors and markers of liver function were also determined in patients and healthy controls. Treatment of HCASMC with patient sera reduced cell proliferation and migration (p < 0.05 vs. healthy controls), whereas apoptosis was unaffected (p = 0.160). Expression of genes associated with a synthetic vascular smooth muscle cell phenotype was decreased in cells stimulated with serum from cirrhotic patients (RBP1, p = 0.001; SPP1, p = 0.003; KLF4, p = 0.004). Platelet-derived growth factor-BB serum concentrations were lower in patients (p = 0.001 vs. controls). The results suggest the presence of circulating factors in patients with alcoholic liver cirrhosis affecting coronary smooth muscle cell growth. These findings may have implications for clinical outcomes following percutaneous coronary revascularization in these patients.

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Transradial Versus Transfemoral Method of Percutaneous Coronary Revascularization for Unprotected Left Main Coronary Artery Disease: Comparison of Procedural and Late-Term Outcomes

JACC Cardiovascular Interventions ◽

10.1016/j.jcin.2010.09.003 ◽

2010 ◽

Vol 3 (10) ◽

pp. 1035-1042 ◽

Cited By ~ 38

Author(s):

Yue-Jin Yang ◽

David E. Kandzari ◽

Zhan Gao ◽

Bo Xu ◽

Ji-Lin Chen ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Left Main Coronary Artery ◽

Coronary Revascularization ◽

Left Main ◽

Main Coronary Artery Disease ◽

Percutaneous Coronary Revascularization ◽

Percutaneous Coronary ◽

Artery Disease

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Abstract 451: Oxygen Regulation of Human Coronary Artery Smooth Muscle Cell Proliferation and Migration

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.35.suppl_1.451 ◽

2015 ◽

Vol 35 (suppl_1) ◽

Author(s):

Mingming Yang ◽

Tomoko Kamishima ◽

Caroline Dart ◽

John M Quayle

Keyword(s):

Cell Proliferation ◽

Smooth Muscle ◽

Cell Migration ◽

Coronary Artery ◽

Cell Viability ◽

Smooth Muscle Cell ◽

Human Coronary Artery ◽

Cell Proliferation And Migration ◽

And Migration ◽

Proliferation And Migration

Introduction: Intimal thickening of blood vessels, a hallmark of several vascular diseases including atherosclerosis and a potential point of therapeutic intervention, is caused by vascular smooth muscle cell proliferation and migration. It has been suggested that oxygen availability in vessels not only regulates behavior of smooth muscle cells but also serves as a trigger that may lead to pathological responses. In this study we determined whether hypoxia elicits proliferative and migratory responses in Human Coronary Artery SMCs (HCASMCs). Methods: Proliferation of HCASMCs was assessed using a 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. SMCs were plated in 96-well plates (n=5), serum starved, and then placed under hypoxic or normoxic conditions for 2, 4 and 6 days (2D/4D/6D) before MTT was added to each well. Absorbance at the wavelength 570 nm was read on an ELISA plate reader, and percent change in cell viability was determined and normalized to control (cell viability under normoxia). Cell migration was characterized by scratch-wound assay. SMCs were seeded in 6 well plates overnight (n=3), then a ‘scratch’ on the cell monolayer was created for each well before putting into different oxygen levels for 4 hours, 12 hours and 24 hours. Images were captured at the beginning and at intervals during cell migration to close the scratch, and the degree of migration was determined by comparing the images. Results: Compared to normoxic condition, cell number changed to 118.1%±1.3% in 5% O 2 (p<0.05) and 98.2%%±1.9% in 1% O 2 after 2D; to 151.9% ±8.5% in 5% O 2 (p<0.001) and 119.4%±5.0% in 1% O 2 (p<0.05) after 4D; and to 163.0%±4.3% in 5% O 2 (p<0.001) and 120.3%±2.2% in 1% O 2 (p<0.05) after 6D. In the cell migration assay, the difference in migration rate between different groups after 4 hours was not obvious, but there was a significant difference after 12 hours (29.3%±1.3% closure in normoxia vs 39.8%±1.9% in 5% O 2 vs 40.9%±3.5% in 1% O 2 , p<0.05) and 24 hours (71.5%±4.4% in normoxia vs 87.2%±2.2% in 5% O 2 vs 87.5%±3.1% in 1% O 2 , p<0.05). Conclusion: Our studies reveal that hypoxia induces both proliferation and migration of HCASMCs.

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