Cardiac and renal fibrosis in chronic cardiorenal syndromes.

In recent years, there has been considerable interest in cellular and tissue responses to injury that result in the deposition of extracellular matrix, collagen, elastic fibers, and the histopathological development of fibrosis. In the myocardium, fibrosis results in many recognizable clinical features, including PR interval prolongation, heart block, bundle branch block, left ventricular dyssynergy, anisotropy, atrial fibrillation, ventricular arrhythmias, systolic and diastolic dysfunction, heart failure, and cardiac death. In the kidneys, fibrosis in the glomerulus leads to glomerular sclerosis, and in the inner cortex and medulla, tubulointerstitial fibrosis leads to a reduction in renal filtration function and rapidly progressive chronic kidney disease. There are a great number of potential early mediators of cellular damage in response to events such as ischemia, neurohormonal activation, biomechanical stretch, and abnormal cell signaling. However, many studies suggest that interstitial cells in both organs, including macrophages, T lymphocytes, fibroblasts, and myofibroblasts, have common communication systems that utilize galectin-3 and transforming growth factor-β that result in the upregulation and proliferation of fibroblasts and myofibroblasts, which produce and secrete procollagen I. Procollagen I cross-links in the extracellular space to form mature collagen, which is a fundamental unit of organ fibrosis. Future research will be concentrating on the pathogenic mechanisms that turn on fibrosis and on therapeutic targets that can either prevent the activation of fibroblasts or limit their repair response to injury.