The mechanisms by which cardiac fibrosis or accumulation of scar tissue in the heart occurs are not fully understood and there are no effective therapies to reverse it. Under the leadership of Dr. Antonio Rodríguez Sinovas, principal investigator of the Cardiovascular Diseases group at the Vall d'Hebron Research Institute (VHIR), researchers have made progress in identifying the involvement of connexin 43 (Cx43) protein which could be key in understanding this process. The mechanisms through which this protein regulates the onset of fibrosis after pressure overload using a murine transgenic model have also been studied.In the work, published in Cells Magazine, Dr. José Martínez González, of the Higher Council for Scientific Research and researchers of the Research Institute of the Hospital de la Santa Creu i Sant Pau, all of them belonging to the CIBER of Cardiovascular Diseases (CIBERCV).Connins are a family of membrane proteins with a characteristic structure that form intercellular channels that contact the cytoplasm of neighboring cells. At the heart, they form plates called "gap junctions" that are pathways of low resistance essential to allow the flow of electric current between the cells. Cx43 is widely distributed in most tissues, including cardiac cells (cardiomyocytes, fibroblasts, and endothelial and smooth muscle cells). Pressure overload results rapidly in hypertrophy, cell death and fibrosisDuring pressure overload, such as in hypertensive patients or with obstruction to the left ventricle exit tract, there is an increase in resistance to the outflow of blood from the heart. This leads, as a compensatory mechanism, to the development of dilatation and cardiac hypertrophy. However, and although cardiac hypertrophy is initially an adaptive process necessary to maintain cardiac output, it progresses rapidly to a pathological condition, resulting in the death of heart cells and fibrosis. The onset of fibrosis is especially relevant as it reduces contractility and causes diastolic dysfunction."Cx43 is an essential protein in cardiac function. It plays a key role in the propagation of electrical impulses and, thus, in the occurrence of ventricular arrhythmias. In addition, it plays a role in the extension of myocardial damage. for ischemia-reperfusion during myocardial infarction, " says Dr. Antonio Rodríguez Sinovas, responsible for the study.To date, there has been conflicting data on its potential role in cardiac healing. "Our work has shown that modulating Cx43 expression is associated with changes in collagen deposition after angiotensin II treatment," he says. "Thus, a marked reduction in Cx43 expression results in a decrease in collagen accumulation relative to that in the control group, thereby improving ventricular remodeling. These data suggest that this protein would be involved in heart healing process, " concludes the researcher.Finally, by means of molecular and cellular biology techniques, the authors have been able to determine that Cx43 may exert its effects on cardiac healing by modulating metalloproteinase activity, as well as inflammatory response and fibroblast activity.