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Endothelial gene responses to homocysteine: relation to atherosclerosis
Hong Li1, Michael S Goligorsky
1Department of Physiology and Biophysics, State University of New York, Stony Brook, N.Y., USA.
Insights
Chronic renal failure patients with hyperhomocysteinemia (HHCy) face higher cardiovascular risks. This study identifies homocysteine-modulated genes involved in endothelial dysfunction and atherosclerosis, offering insights into disease mechanisms.
Area of Science:
- Cardiovascular Science
- Nephrology
- Molecular Biology
Background:
- Chronic renal failure (CRF) significantly elevates cardiovascular mortality risk, partly due to accelerated atherosclerosis.
- Hyperhomocysteinemia (HHCy), a common condition in CRF patients, is an established risk factor for atherosclerosis, but its mechanisms are unclear.
Purpose of the Study:
- To investigate the molecular mechanisms by which hyperhomocysteinemia contributes to atherosclerosis in the context of chronic renal failure.
- To identify genes modulated by homocysteine in endothelial cells relevant to cardiovascular pathology.
Main Methods:
- Utilized a cardiovascular cDNA microarray to screen the expression of 600 cardiovascular-relevant genes.
- Analyzed gene expression in human umbilical endothelial cells exposed to homocysteine.
- Classified differentially expressed genes into functional clusters: endothelial motility, signaling, and lipid metabolism.
Main Results:
- Identified several genes whose expression is modulated by homocysteine in endothelial cells.
- Observed differential gene expression patterns related to endothelial motility, intracellular signaling, and lipid metabolism.
- These findings suggest homocysteine impacts endothelial function and lipid processing.
Conclusions:
- Homocysteine significantly affects gene expression in endothelial cells, impacting key cellular functions.
- The identified homocysteine-modulated genes provide potential molecular targets for understanding and treating atherosclerosis in CRF patients.
- This research sheds light on the pathophysiological role of HHCy in endothelial dysfunction and atherosclerotic development.
Abstract:
Chronic renal failure is associated with a 20-fold increased risk of cardiovascular mortality, in part due to accelerated atherosclerosis. Hyperhomocysteinemia (HHCy) is common in patients with chronic renal failure. It has been established that HHCy is an independent and graded risk factor for atherosclerosis, though the mechanisms responsible for it remain obscure. Using the cardiovascular cDNA microarray approach, we screened the expression of 600 cardiovascular relevant genes in human umbilical endothelial cells and identified a number of homocysteine-modulated genes. These differentially displayed genes were classified according to the functional outcome of their encoded proteins: endothelial motility cluster, signaling cluster, and lipid metabolism cluster. The results may be relevant to understanding the mechanisms underlying the pathophysiological effects of HHCy, particularly those leading to endothelial dysfunction and the pathogenesis of atherosclerosis.