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Homocyst(e)ine and heart disease: pathophysiology of extracellular matrix
1Department of Physiology and Biophysics and Center of Excellence in Cardiovascular & Renal Research, The University of Mississippi Medical Center, Jackson 39216-4505, USA.
Insights
High homocysteine levels contribute to cardiovascular fibrosis and adverse extracellular matrix remodeling, potentially leading to heart failure. Understanding these mechanisms is crucial for treating heart disease.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
- Pathology
Background:
- Occlusive coronary artery disease significantly contributes to cardiovascular morbidity and mortality.
- The mechanisms underlying fibrous plaque formation in atherosclerosis remain poorly understood.
- Elevated plasma homocysteine (hyperhomocysteinemia) is an independent risk factor for hypertension and fibrotic heart disease.
Purpose of the Study:
- To investigate the role of tissue homocystine in cardiovascular fibrosis and extracellular matrix (ECM) remodeling.
- To elucidate the mechanisms by which hyperhomocysteinemia contributes to adverse cardiac outcomes.
- To explore the link between tissue redox state and cardiovascular fibrosis in various heart conditions.
Main Methods:
- In vivo and in vitro physiological, morphological, cellular, biochemical, and molecular experiments were conducted.
- Studies focused on the effects of elevated homocysteine on cardiovascular tissues.
- Analysis included assessment of ECM components and cellular responses.
Main Results:
- Tissue homocystine was found to induce cardiovascular fibrosis and adverse ECM remodeling.
- Elevated homocysteine contributes to the accumulation of ECM components like fibrillar collagen in atherosclerotic lesions.
- These changes create an environment that sequels oxidized LDL, macrophages, and foam cells, forming atherosclerotic lesions.
Conclusions:
- Tissue homocystine plays a significant role in promoting cardiovascular fibrosis and adverse ECM remodeling.
- Hyperhomocysteinemia may lead to heart failure through a redox-receptor pathway.
- Changes in tissue redox state are implicated in the development of cardiovascular fibrosis associated with arteriosclerosis, atherosclerosis, hypertension, and coronary heart disease.
Abstract:
Occlusive coronary artery disease is an important factor of cardiovascular morbidity and mortality. The rupture of the thin fibrous cap of the atheroma may be one of the causes of acute coronary syndrome, however, the mechanism of formation of fibrous plaque are poorly understood. Elevation of plasma homocysteine, hyperhomocystinemia, H(e), has emerged as an independent risk factor for hypertension and fibrotic heart disease. The extracellular matrix (ECM) components, particularly fibrillar collagen, are elevated in the atherosclerotic lesions and are the essential integral element in holding the oxidized low density lipoproteins (LDL), homocystine, macrophage and foam cells in milieu, constituting the primary atherosclerotic and secondary restenotic lesions. In vivo and in vitro physiological, morphological, cellular, biochemical and molecular experiments have suggested the role of tissue homocystine in cardiovascular fibrosis and adverse ECM remodeling following H(e). The tissue homocystine induces cardiovascular fibrosis and may lead to heart failure via the redox-receptor pathway. The underlying cause and mechanism of cardiovascular fibrosis associated with arteriosclerosis, atherosclerosis, hypertension and coronary heart disease, involve changes in the levels of tissue redox state.