Abstract
Cardiovascular diseases, such as atherosclerosis and aortic valve sclerosis (AVS) are driven by inflammation induced by a variety of stimuli, including low-density lipoproteins (LDL), reactive oxygen species (ROS), infections, mechanical stress, and chemical insults. Fibrosis is the process of compensating for tissue injury caused by chronic inflammation. Fibrosis is initially beneficial and maintains extracellular homeostasis. However, in the case of AVS and atherosclerosis, persistently active resident fibroblasts, myofibroblasts, and smooth muscle cells (SMCs) perpetually remodel the extracellular matrix under the control of autocrine and paracrine signaling from the immune cells. Myofibroblasts also produce pro-fibrotic factors, such as transforming growth factor-β1 (TGF-β1), angiotensin II (Ang II), and interleukin-1 (IL-1), which allow them to assist in the activation and migration of resident immune cells. Post wound repair, these cells undergo apoptosis or become senescent; however, in the presence of unresolved inflammation and persistence signaling for myofibroblast activation, the tissue homeostasis is disturbed, leading to excessive extracellular matrix (ECM) secretion, disorganized ECM, and thickening of the affected tissue. Accumulating evidence suggests that diverse mechanisms drive fibrosis in cardiovascular pathologies, and it is crucial to understand the impact and contribution of the various mechanisms for the control of fibrosis before the onset of a severe pathological consequence.