Pharmacological Inhibition of Focal Adhesion Kinase Attenuates Cardiac Fibrosis in Mice Cardiac Fibroblast and Post-Myocardial-Infarction Models

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Guang-Pu FanXu Wang

Abstract

To investigate the role of focal adhesion kinase (FAK)-mediated signaling in hypoxia-induced cardiac fibroblasts (CFs) differentiation and cardiac fibrosis post-myocardial infarction (MI) on a mice model. CFs of neonatal C57BL/6 mice were treated under normoxic, hypoxic, or hypoxic+PP2 (known as a Src kinase family inhibitor) conditions. Gene expressions of FAK, alpha-smooth muscle actin (α-SMA) and collagen type I alpha 1 (Col1α1), or α-SMA and vimentin levels were performed by RT-PCR and immunofluorescence staining, respectively. Thirty mice were surgically treated into Sham (n=7) and MI (n=23) groups; and FAK inhibitor PF-562271 was given to six survivor MI mice (as PF group, from 15 survivors). Heart function and collagenous tissues were examined by echocardiography, as well as by Masson‘s trichrome and Sirius red staining, respectively. Type I collagen, FAK protein, mTOR, ERK1/2, AKT, P70S6K and phospho-FAK levels were also analyzed. FAK inhibition with PP2 significantly decreased CFs differentiation and collagen synthesis under hypoxia treatment. In vivo, PF-562271 treatment resulted in fibrosis attenuation; however, deteriorated heart function of MI mice could not be significantly improved. PF-562271 may affect phospho-m...Continue Reading

Citations

Nov 3, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jacopo Meldolesi
Apr 6, 2017·Journal of Cellular and Molecular Medicine·Elena Revuelta-LópezVicenta Llorente-Cortés
Dec 9, 2017·Frontiers in Pharmacology·Xiaoyi LiRuixin Zhu
Mar 12, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Amanda K WheatonKevin K Kim
Oct 12, 2018·American Journal of Physiology. Renal Physiology·Eoghainín Ó hAinmhireBenjamin D Humphreys
Jan 20, 2018·Current Rheumatology Reports·Alba Santos, David Lagares
Nov 30, 2019·Experimental and Therapeutic Medicine·Pingheng ZhangRuikai Zong
Dec 4, 2019·Nature Reviews. Rheumatology·Boris Hinz, David Lagares
Nov 3, 2020·Cardiovascular Research·Nikolaos G Frangogiannis
Jul 30, 2018·Molecular Aspects of Medicine·Nikolaos G Frangogiannis
May 4, 2020·The Journal of Thoracic and Cardiovascular Surgery·Brittany A PotzFrank W Sellke

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiac Remodeling

Cardiac remodeling in response to a myocardial infarction is characterized by progressive ventricular dilatation, cardiac hypertrophy, fibrosis, and deterioration of cardiac performance. Discover the latest research on Cardiac Remodeling here.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Cardiomegaly

Cardiomegaly, known as an enlarged heart, is a multifactorial disease with different pathophysiological mechanisms. Hypertension, pregnancy, exercise-induced and idiopathic causes are some mechanisms of cardiomegaly. Discover the latest research of cardiomegaly here.

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.

Related Papers

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Yonglan ZhouXinli Li
Cellular & Molecular Biology Letters
Joanna MiloszewskaPrzemyslaw Janik
International Journal of Clinical and Experimental Pathology
Jin LiQizhu Tang
© 2021 Meta ULC. All rights reserved