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The role of fibroblasts and the extracellular matrix in cardiac remodeling and regeneration

Luit, R.J. van (2015) The role of fibroblasts and the extracellular matrix in cardiac remodeling and regeneration. Bachelor's Thesis, Biology.

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The low turnover number of cardiomyocytes (CM) contributes to the progressive adverse effects after heart injury. Much research focusses on the proliferation of CM. However, cardiac fibroblasts may play a major role in the process of cardiac regeneration since they make up for half of the total cell number in the myocardium. Therefore, in this review, the regeneration of myocardium is discussed in a broader perspective by investigating the interactions between fibroblasts, macrophages and CMs. Under pathological conditions, the extracellular matrix (ECM) stiffens, and type I-receptor transforming growth factor (TGFβ1) bioavailability and signalling increases, which stimulate fibroblasts to differentiate into myofibroblasts. These α- smooth muscle actin (SMA) expressing fibroblasts, show an increased production of ECM proteins in response to TGFβ1 and increased stiffness. Macrophages play a role in these processes via angiotensin II (ATII) signalling and TGFβ1 production. MC-fibroblast interactions are complex and involve many types of signal transduction including TGFβ1, FGF2 and FGF16, Notch signalling, indirect signalling via the ECM and signalling via gap junctions between both cell types. Recent developments regarding cardiac research showed increased CM proliferation and decreased formation of chronic scars in neonatal rodents after cardiac injury. Additionally, evidence exists for increased CM proliferation in young humans compared to adult, indicating a different role for fibroblasts during early stages of life compared to adulthood. Some of these differences can be explained by altered MC-fibroblast interactions. This review provides recent insights in the relations between different cell types involved in cardiac remodelling and discusses some recent developments in cardiac regeneration in a broader perspective.

Item Type: Thesis (Bachelor's Thesis)
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 15 Feb 2018 08:04
Last Modified: 15 Feb 2018 08:04

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