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Aging, ion channel expression, and vascular function
Ligia Toro1, Jure Marijic, Kazuhide Nishimaru
1Department of Anesthesiology, Department of Molecular and Medical Pharmacology, Brain Research Institute, School of Medicine, University of California Los Angeles, Los Angeles, CA 90095-1778, USA. ltoro@ucla.edu
Insights
Aging stiffens coronary arteries by altering key ion channels, increasing the risk of heart attack and heart failure in older adults. Understanding these vascular changes is crucial for developing new treatments.
Area of Science:
- Cardiovascular Physiology
- Vascular Aging
- Molecular Cardiology
Background:
- Cardiovascular disease is a leading cause of death, with aging as a primary risk factor.
- Aging alters coronary arteries, increasing stiffness and contractile activity, risking vasospasm, ischemia, and heart failure.
- K+ channels in vascular smooth muscle cells regulate coronary arterial tone.
Purpose of the Study:
- To investigate the molecular mechanisms of vascular aging in the coronary circulation.
- To understand the role of K+ channels, specifically BKCa channels, in age-related coronary artery dysfunction.
- To identify changes in coronary artery physiology that increase the risk of cardiovascular events in the elderly.
Main Methods:
- Analysis of changes in BKCa channel density in coronary smooth muscle with aging.
- Assessment of nitric oxide (NO) release from the endothelium in aged coronary arteries.
- Evaluation of responses to constrictor and dilator factors in aged versus young coronary arteries.
Main Results:
- Aging reduces the density of the alpha-subunit of BKCa channels in coronary smooth muscle.
- Endothelial nitric oxide (NO) release is decreased, while responses to constrictor factors are increased with aging.
- These molecular and cellular changes lead to increased coronary artery excitability and contractility.
Conclusions:
- Aging induces significant remodeling of coronary arteries, affecting ion channel function and endothelial signaling.
- These age-related vascular changes contribute to increased risk of coronary vasospasm, myocardial ischemia, and infarction in the elderly.
- Targeting these molecular mechanisms may offer strategies to preserve cardiovascular health in aging populations.
Abstract:
Cardiovascular disease remains the leading cause of death in the United States, and aging is one of the main risk factors for its development. Coronary arteries nurture the heart, but as age progresses, they suffer changes that make them stiffer, thicker, and with higher spontaneous contractile activity. Even in the absence of pathological atherosclerotic lesions, these changes make the coronary arteries at risk for vasospasm and the individual at risk for myocardial ischemia and heart failure. Thus, knowledge of the molecular mechanisms involved in the vascular physiology, disease, and aging of the coronary circulation is required to develop strategies to preserve the quality of life of an increasingly aging population. One of the key factors that regulate coronary arterial tone is the activity of K+ channels in the vascular smooth muscle cells (SMCs). In particular, voltage-dependent and Ca(2+)-activated K+ (BKCa) channels, which are abundant in the coronary SMCs, are targets of vasoconstrictors and vasorelaxants, and play a key role in determining arterial tone and diameter. Aging induces a reduction in the density of the alpha-subunit of BKCa channels in coronary smooth muscle, lowers baseline endothelial release of the relaxant nitric oxide (NO), and increases the response to endothelial constrictor factors and K+. Thus, aging induces the remodeling of important proteins involved in the excitability and contractility of the coronary circulation. Altogether, these changes increase the risk of coronary artery vasospasm, myocardial ischemia, and infarct in the elderly.