Interesting new work from Dr. Jeffrey Molkentin's Lab published in The Journal of Clinical Investigation- Insight, utilized B-CHP to evaluate the effect that Hsp47 deletion has on the collagen production of myocardiocytes (top), endothelial cells (middle), and myofibroblasts (bottom) after transverse aortic constriction (TAC) surgery (a pressure overload model). Their results show that although all three cell types could produce collagen, without Hsp47, only the myofibroblast group showed a drastic decrease in collagen production after TAC, suggesting that myofibroblasts are primarily responsible for collagen production after acute cardiac injury or chronic heart diseases. The right column of images has Hsp47 deletion.

Abstract: Collagen production in the adult heart is thought to be regulated by the fibroblast, although cardiomyocytes and endothelial cells also express multiple collagen mRNAs. Molecular chaperones are required for procollagen biosynthesis, including heat shock protein 47 (Hsp47). To determine the cell types critically involved in cardiac injury–induced fibrosis the Hsp47 gene was deleted in cardiomyocytes, endothelial cells, or myofibroblasts. Deletion of Hsp47 from cardiomyocytes during embryonic development or adult stages, or deletion from adult endothelial cells, did not affect cardiac fibrosis after pressure overload injury. However, myofibroblast-specific ablation of Hsp47 blocked fibrosis and deposition of collagens type I, III, and V following pressure overload as well as significantly reduced cardiac hypertrophy. Fibroblast-specific Hsp47-deleted mice showed lethality after myocardial infarction injury, with ineffective scar formation and ventricular wall rupture. Similarly, only myofibroblast-specific deletion of Hsp47 reduced fibrosis and disease in skeletal muscle in a mouse model of muscular dystrophy. Mechanistically, deletion of Hsp47 from myofibroblasts reduced mRNA expression of fibrillar collagens and attenuated their proliferation in the heart without affecting paracrine secretory activity of these cells. The results show that myofibroblasts are the primary mediators of tissue fibrosis and scar formation in the injured adult heart, which unexpectedly affects cardiomyocyte hypertrophy.


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