Mechanisms of cardiac collagen deposition in experimental models and human disease

• Published in: Translational research : the journal of laboratory and clinical medicine Vol. 209; pp. 138 - 155
• Main Authors: Cowling, Randy T., Kupsky, Daniel, Kahn, Andrew M., Daniels, Lori B., Greenberg, Barry H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2019
• Subjects: Animals; Biomarkers - metabolism; Collagen - metabolism; Disease Models, Animal; Fibrosis; Heart Diseases - metabolism; Heart Diseases - pathology; Humans; Myocardium - metabolism; EDA; Col III; MRTF-A; MRI; HFpEF; HFrEF; Gal-3; CTGF; α-SMA; hsTn; miRNA; TGF-β; MI; EndMT; ST2L; IL; CMR; AT1R; LGE; sST2; MAPK; Col I; EMT; Ang II; ECM; COL1A1; ST2; MMP; COL3A1; ET-1; LOX; TAC; Tcf21; ECV; LAP; CITP; TIMP
• ISSN: 1931-5244; 1878-1810
• DOI: 10.1016/j.trsl.2019.03.004

The inappropriate deposition of extracellular matrix within the heart (termed cardiac fibrosis) is associated with nearly all types of heart disease, including ischemic, hypertensive, diabetic, and valvular. This alteration in the composition of the myocardium can physically limit cardiomyocyte contractility and relaxation, impede electrical conductivity, and hamper regional nutrient diffusion. Fibrosis can be grossly divided into 2 types, namely reparative (where collagen deposition replaces damaged myocardium) and reactive (where typically diffuse collagen deposition occurs without myocardial damage). Despite the widespread association of fibrosis with heart disease and general understanding of its negative impact on heart physiology, it is still not clear when collagen deposition becomes pathologic and translates into disease symptoms. In this review, we have summarized the current knowledge of cardiac fibrosis in human patients and experimental animal models, discussing the mechanisms that have been deduced from the latter in relation to the former. Because assessment of the extent of fibrosis is paramount both as a research tool to further understanding and as a clinical tool to assess patients, we have also summarized the current state of noninvasive/minimally invasive detection systems for cardiac fibrosis. Albeit not exhaustive, our aim is to provide an overview of the current understanding of cardiac fibrosis, both clinically and experimentally.