Loss of talin in cardiac fibroblasts results in augmented ventricular cardiomyocyte hypertrophy in response to pressure overload

Natalie A. Noll, Lance A. Riley, Christy S. Moore, Lin Zhong, Mathew R. Bersi, James D. West, Roy Zent, W. David Merryman

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Pressure overload of the heart is characterized by concentric hypertrophy and interstitial fibrosis. Cardiac fibroblasts (CFs) in the ventricular wall become activated during injury and synthesize and compact the extracellular matrix, which causes interstitial fibrosis and stiffening of the ventricular heart walls. Talin1 (Tln1) and Talin2 (Tln2) are mechanosensitive proteins that participate in focal adhesion transmission of signals from the extracellular environment to the actin cytoskeleton of CFs. The aim of the present study was to determine whether the removal of Tln1 and Tln2 from CFs would reduce interstitial fibrosis and cardiac hypertrophy. Twelve-week-old male and female Tln2-null (Tln2-/-) and Tln2-null, CF-specific Tln1 knockout (Tln2-/-;Tln1CF-/-) mice were given angiotensin-II (ANG II) (1.5 mg/kg/day) or saline through osmotic pumps for 8 wk. Cardiomyocyte area and measures of heart thickness were increased in the male ANG II-infused Tln2-/-;Tln1CF-/-mice, whereas there was no increase in interstitial fibrosis. Systolic blood pressure was increased in the female Tln2-/-;Tln1CF-/-mice after ANG II infusion compared with the Tln2-/-mice. However, there was no increase in cardiac hypertrophy in the Tln2-/-;Tln1CF-/-mice, which was seen in the Tln2-/-mice. Collectively, these data indicate that in male mice, the absence of Tln1 and Tln2 in CFs leads to cardiomyocyte hypertrophy in response to ANG II, whereas it results in a hypertrophy-resistant phenotype in female mice. These findings have important implications for the role of mechanosensitive proteins in CFs and their impact on cardiomyocyte function in the pathogenesis of hypertension and cardiac hypertrophy.

Original languageEnglish
Pages (from-to)H857-H866
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume322
Issue number5
DOIs
StatePublished - May 2022

Keywords

  • fibroblast
  • hypertrophy
  • talin

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