At autopsy, the heart of an 80-year-old man has a small left ventricular cavity and thickening of the left ventricle walls, which measure 1.7 cm (normal: 0.7-1.1) at the posterior and septal wall locations. Microscopic examination shows diffusely enlarged cardiomyocytes, with prominent nuclei evident at low power. Increased expression of which of the following substances most likely contributed to these pathologic findings?
The pathology evaluation of this patient's heart shows uniformly thickened left ventricle walls (resulting in decreased ventricular cavity size) and enlarged cardiomyocytes with highly visible nuclei, which are consistent with concentric left ventricular hypertrophy (LVH). This condition commonly results from chronic hypertension, which leads to increased local expression of the vasoconstrictors angiotensin II and endothelin in the heart; these 2 mediators likely have a prominent role in the development of LVH.
Although all medications that lower systemic blood pressure (eg, calcium channel blockers, thiazide diuretics) can reduce concentric LVH, angiotensin II receptor blockers provide the greatest reduction in remodelling, suggesting a role of angiotensin II in the development of LVH that is independent of blood pressure. Endothelin receptor blockers (eg, bosentan) are not typically used to treat systemic hypertension, but they may reduce right ventricular hypertrophy when used to treat pulmonary arterial hypertension.
Local angiotensin II production also likely has a prominent role in the development of eccentric LVH in response to left ventricular volume overload.
(Choice A) A compensatory increase in adenosine expression occurs in response to myocardial ischemia and reperfusion of the heart. Adenosine dilates blood vessels, especially coronary arteries, to improve circulation; it does not contribute to LVH.
(Choice C) Calcitonin gene-related peptide (CGRP) is a neuropeptide that is a potent vasodilator, and it may have a role in protecting the heart from heart failure and LVH. CGRP blockers are used to prevent migraines by reducing the size of abnormally dilated blood vessels in the brain.
(Choice D) Interleukin-1 is a proinflammatory cytokine implicated in atherosclerosis development; high levels are expected in coronary artery disease but not in LVH. Interleukin-1 blockers can be used to treat autoimmune inflammatory conditions (eg, rheumatoid arthritis).
(Choice E) Nitric oxide synthase is an enzyme that catalyzes the production of nitric oxide (a potent vasodilator). Nitric oxide is protective against LVH, and relatively low levels of nitric oxide synthase are expected with LVH.
Educational objective:
Concentric left ventricular hypertrophy (LVH) is a common complication of chronic hypertension, characterized by uniformly thickened ventricular walls and enlarged cardiomyocytes and nuclei. The vasoconstrictors angiotensin II and endothelin likely have a prominent role in the development of concentric LVH independent of their effects on blood pressure. Angiotensin II receptor blockers are more effective than other antihypertensive agents in reducing LVH.