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YAP and TAZ in Vascular Smooth Muscle Confer Protection Against Hypertensive Vasculopathy

Daoud, Fatima LU ; Arévalo Martinez, Marycarmen LU ; Holmberg, Johan LU ; Alajbegovic, Azra LU ; Ali, Neserin LU orcid ; Rippe, Catarina LU ; Swärd, Karl LU and Albinsson, Sebastian LU (2022) In Arteriosclerosis, Thrombosis, and Vascular Biology 42(4). p.428-443
Abstract

Background: Hypertension remains a major risk factor for cardiovascular diseases, but the underlying mechanisms are not well understood. We hypothesize that appropriate mechanotransduction and contractile function in vascular smooth muscle cells are crucial to maintain vascular wall integrity. The Hippo pathway effectors YAP (yes-associated protein 1) and TAZ (WW domain containing transcription regulator 1) have been identified as mechanosensitive transcriptional coactivators. However, their role in vascular smooth muscle cell mechanotransduction has not been investigated in vivo. Methods: We performed physiological and molecular analyses utilizing an inducible smooth muscle-specific YAP/TAZ knockout mouse model. Results: Arteries... (More)

Background: Hypertension remains a major risk factor for cardiovascular diseases, but the underlying mechanisms are not well understood. We hypothesize that appropriate mechanotransduction and contractile function in vascular smooth muscle cells are crucial to maintain vascular wall integrity. The Hippo pathway effectors YAP (yes-associated protein 1) and TAZ (WW domain containing transcription regulator 1) have been identified as mechanosensitive transcriptional coactivators. However, their role in vascular smooth muscle cell mechanotransduction has not been investigated in vivo. Methods: We performed physiological and molecular analyses utilizing an inducible smooth muscle-specific YAP/TAZ knockout mouse model. Results: Arteries lacking YAP/TAZ have reduced agonist-mediated contraction, decreased myogenic response, and attenuated stretch-induced transcriptional regulation of smooth muscle markers. Moreover, in established hypertension, YAP/TAZ knockout results in severe vascular lesions in small mesenteric arteries characterized by neointimal hyperplasia, elastin degradation, and adventitial thickening. Conclusions: This study demonstrates a protective role of YAP/TAZ against hypertensive vasculopathy.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adventitia, Compliance, Hyperplasia, Muscle, Neointima, Smooth, Vascular
in
Arteriosclerosis, Thrombosis, and Vascular Biology
volume
42
issue
4
pages
16 pages
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:85127895535
  • pmid:35196875
ISSN
1079-5642
DOI
10.1161/ATVBAHA.121.317365
language
English
LU publication?
yes
id
d7e42227-edc5-46d1-a47b-48368350eef2
date added to LUP
2022-06-10 09:39:35
date last changed
2025-03-21 21:40:39
@article{d7e42227-edc5-46d1-a47b-48368350eef2,
  abstract     = {{<p>Background: Hypertension remains a major risk factor for cardiovascular diseases, but the underlying mechanisms are not well understood. We hypothesize that appropriate mechanotransduction and contractile function in vascular smooth muscle cells are crucial to maintain vascular wall integrity. The Hippo pathway effectors YAP (yes-associated protein 1) and TAZ (WW domain containing transcription regulator 1) have been identified as mechanosensitive transcriptional coactivators. However, their role in vascular smooth muscle cell mechanotransduction has not been investigated in vivo. Methods: We performed physiological and molecular analyses utilizing an inducible smooth muscle-specific YAP/TAZ knockout mouse model. Results: Arteries lacking YAP/TAZ have reduced agonist-mediated contraction, decreased myogenic response, and attenuated stretch-induced transcriptional regulation of smooth muscle markers. Moreover, in established hypertension, YAP/TAZ knockout results in severe vascular lesions in small mesenteric arteries characterized by neointimal hyperplasia, elastin degradation, and adventitial thickening. Conclusions: This study demonstrates a protective role of YAP/TAZ against hypertensive vasculopathy. </p>}},
  author       = {{Daoud, Fatima and Arévalo Martinez, Marycarmen and Holmberg, Johan and Alajbegovic, Azra and Ali, Neserin and Rippe, Catarina and Swärd, Karl and Albinsson, Sebastian}},
  issn         = {{1079-5642}},
  keywords     = {{Adventitia; Compliance; Hyperplasia; Muscle; Neointima; Smooth; Vascular}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{4}},
  pages        = {{428--443}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Arteriosclerosis, Thrombosis, and Vascular Biology}},
  title        = {{YAP and TAZ in Vascular Smooth Muscle Confer Protection Against Hypertensive Vasculopathy}},
  url          = {{http://dx.doi.org/10.1161/ATVBAHA.121.317365}},
  doi          = {{10.1161/ATVBAHA.121.317365}},
  volume       = {{42}},
  year         = {{2022}},
}