Pathogenesis of Heart Disease and Targets for Gene Therapy

Myocardial ischemia associated with CAD is the primary cause of myocardial failure (60). Systemic hypertension, disorders of lipid metabolism, and diabetes are the predominant predisposing factors for CAD (2). Acute ischemic events, if sufficiently prolonged, will lead to irreversible damage and infarction, underlined by alterations in membrane fluidity, intracellular hydrogen ion concentration and metabolic activity, and eventual cell death, resulting in arrhythmia and impaired pump function (61). Paradoxically, reoxygenation of the ischemic myocardium induces a robust increase in reactive oxygen species (ROS), which triggers a profound inflammatory response that may exacerbate the damage initiated during ischemia (61-63). In time, the left ventricle undergoes a process of remodeling characterized by myocyte hypertrophy, interstitial fibrosis, chamber dilatation, and increased propensity for contractile dysfunction that ultimately leads to ventricular failure (64). The remodeling process is complex and highly dependent on the activity of matrix metalloproteinases (MMPs), a group of zinc-dependent proteases that are involved in extracellular matrix degradation (65). Chronic ischemic heart disease is also characterized by heightened inflammatory state and oxidative stress (66,67). The increased levels of proinflammatory cytokines depress myocardial contractility and activate neurohormonal systems such as the renin-angiotensin system, which promote ventricular fibrosis and remodeling.

Your Heart and Nutrition

Your Heart and Nutrition

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