A 62-year-old man dies suddenly in his sleep. The patient had a history of type 2 diabetes mellitus and hypertension, and he smoked a pack of cigarettes daily for 25 years. His adherence to medical care was poor. Autopsy is performed, and a histologic section of his left ventricular myocardium is shown below: Which of the following directly promotes the formation of the tissue indicated by the arrow?

Question

A 62-year-old man dies suddenly in his sleep.  The patient had a history of type 2 diabetes mellitus and hypertension, and he smoked a pack of cigarettes daily for 25 years.  His adherence to medical care was poor.  Autopsy is performed, and a histologic section of his left ventricular myocardium is shown below:  Which of the following directly promotes the formation of the tissue indicated by the arrow?

Quizplus · Accepted Answer

11ec160b_38dd_961c_9249_2bcb2aaa520b_MD0001_00 This patient's autopsy shows a large area of fibrosis replacing myocardium, consistent with scar tissue from a resolved myocardial infarction (MI). Myocardial tissue damage due to ischemia initiates a series of changes that are analogous to cutaneous wound healing: Inflammation: Hours to days post-MI, neutrophils and macrophages remove necrotic tissue and release cytokines and growth factors that initiate tissue proliferation. Proliferation: Days to weeks post-MI, transforming growth factor-beta (TGF-β) and other anti-inflammatory cytokines downregulate the inflammatory response and stimulate fibroblast migration and proliferation, causing extensive type I and III collagen deposition. Remodeling: Weeks to months post-MI, TGF-β also stimulates production of matrix metalloproteinases (MMPs) that facilitate collagen remodeling (ie, fiber rearrangement) and crosslinking to form dense scar tissue. Because cardiac myocytes are terminally differentiated and do not proliferate to a significant degree in response to injury, areas of extensive myocardial fibrosis do not regain the electrical properties of normal myocardium. Therefore, patients with large scars from previous MIs are at increased risk of sudden death due to arrhythmia. (Choice A) Endothelium-derived relaxing factor (ie, nitric oxide), causes vasodilation via stimulation of vascular smooth muscle relaxation. Although local synthesis of nitric oxide is increased post-MI, it contributes to reperfusion rather than fibrosis at the site of injury. (Choice B) Interferon-beta (IFN-β) is released by a variety of cells, including macrophages, and functions as an anti-inflammatory cytokine that reduces the formation of fibrotic tissue. (Choices C and E) Interleukin-8 and tumor necrosis factor-alpha (TNF-α) are proinflammatory cytokines that stimulate the recruitment and activation of other immune cells (eg, neutrophils). However, neither directly promotes fibrosis in a healing wound. Educational objective: After myocardial infarction, transforming growth factor-beta (TGF-β) reduces inflammation and promotes tissue remodeling due to fibroblast proliferation and collagen deposition, resulting in fibrosis in the area damaged by ischemia. Abnormal myocardium at the scar border can predispose patients to sudden death as a result of arrhythmia.

A 62-Year-Old Man Dies Suddenly in His Sleep