Complosome Activation after Myocardial Infarction in a Murine Model of Permanent LAD Ligation.

Abstract

It has been widely accepted for many years that the essential components of the complement cascade (ComC), including C3 and C5 proteins, are produced solely in the liver and released into circulation after synthesis. However, recent evidence shows that complement components are also expressed in other cell types, including human cardiomyocytes. Moreover, a new regulatory loop was identified in lymphocytes that regulates immune responses and metabolism, named the "Complosome." Following this significant discovery, the Complosome has been shown to play a role in the trafficking and metabolism of hematopoietic stem/progenitor cells (HSPCs) and is expressed in several types of bone marrow (BM) resident stem cells. ComC has been studied in various models of tissue and organ injury and regeneration. However, most of these studies did not distinguish between the role of systemic, liver-derived circulating complement in the blood and the complement expressed as a "Complosome" inside cells. Since Complosome is expressed in several types of stem cells that could influence the clinical outcome of myocardial infarction (MI), this distinction is important because intracellular components of the ComC may have beneficial roles in cell survival, growth, differentiation, and trafficking of stem and progenitor cells. We report herein the systemic activation of the Complosome in the heart and hematopoietic tissues in a murine model of myocardial infarction (MI).