Fibrosis

The deposition of extracellular matrix in disease stress tissue occurs in many organs and disease contexts.

Stress triggers multiple cell types, including fibroblasts and myofibroblasts, ultimately leading to the elaboration of excess extracellular matrix.

Fibrosis impairs tissue function over time.

There are fibrogenic cells within each tissue: resident perivascular mesenchymal cells, pericytes and fibroblasts, which have the ability to transform or activate through tissue injury into contractile fibrogenic cells that secrete scar molecules, primarily interstitial collagen and specialized glycoloproteins, to create a dense network that can interfere with organ function.

There are four phases of fibrotic response: first the initiation of the response by the primary injury to the organ, second phase is the activation of effector cells, the third phase is elaboration of extracellular matrix, and the fourth phase is the deposition of extracellular metrics promoting progression to fibrosis and in the organ failure.

Fibrosis is a complex process involving multiple different types of cells with involvement of specific molecular pathways.

Cellular constituents include macrophages, T cells, epithelial cells, fibrogenic effector cells, endothelial cells, fibroblasts, myofibroblasts, bone marrow cells, fibrocytes.

Transforming growth factor beta pathway (TGF-Beta) is important in the development of all types of fibrosis..

Fibrosis in the heart is divided into two types: reactive and replacement.

Reactive fibrosis occurs in perivascular spaces, similar to fibrogenic responses in other tissues.

Replacement fibrosis occurs at sites of cardiomyocyte loss.

Cardiac fibrosis helps to maintain tissue integrity during myocardial infarction, but chronic fibrosis impairs mechanical function and perturbs electrical excitation and repolarization in the heart.

Ventricular septa collagenization contributed to arrhythmias  by disrupting continuous slow conduction and triggering spontaneous activity through electrically coupled myofibroblasts.

Parenchymal fibrosis is dynamic and can progress or resorb.

T cell chimeric antigen production techniques ate targeting fibrosis.