ArticleCardiovascular research2017
Inhibition of SRF/myocardin reduces aortic stiffness by targeting vascular smooth muscle cell stiffening in hypertension.
Article in Cardiovascular research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 76 citations in OpenAlex.
- Phosphoproteomics in Vascular Biology and Disease: Illuminating Signaling in the Vessel.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Structural and Signaling Mechanisms of Aortic Wall Failure in Heritable Thoracic Aortic Disease.Cells · 2026Review
- FGF12 induces aberrant mechanosignaling in aortic smooth muscle cells during thoracic aortic aneurysm formation in Marfan syndrome mice.Experimental & molecular medicine · 2026Article
- Finite Element Analysis of a PTFE Felt Interposition Pad for Relieving Vascular Compression of the Trigeminal Nerve.Applied bionics and biomechanics · 2026Article
- Single-cell landscape of mouse lungs exposed to intermittent hypoxia.Respiratory research · 2025Article
- The universal role of adaptive transcription in health and disease.The FEBS journal · 2025Review
- New insights into the pharmacological inhibition of SRF activity: Key inhibitory targets and mechanisms.Vascular pharmacology · 2024Review
- PAI-1 Regulates the Cytoskeleton and Intrinsic Stiffness of Vascular Smooth Muscle Cells.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Recent advances in serum response factor posttranslational modifications and their therapeutic potential in cardiovascular and neurological diseases.Vascular pharmacology · 2024Review
- Ovariectomy-Induced Arterial Stiffening Differs From Vascular Aging and Is Reversed by GPER Activation.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Human umbilical cord/placenta mesenchymal stem cell conditioned medium attenuates intestinal fibrosis in vivo and in vitro.Stem cell research & therapy · 2024Article
- Mural Serum Response Factor (SRF) Deficiency Provides Insights into Retinal Vascular Functionality and Development.International journal of molecular sciences · 2023Article
- Epigenetic Signatures in Arterial Hypertension: Focus on the Microvasculature.International journal of molecular sciences · 2023Review
- SENP2 Promotes VSMC Phenotypic Switching via Myocardin De-SUMOylation.International journal of molecular sciences · 2022Article
- Disparate biomechanical properties of the aorta in non-aneurysmal and aneurysmal mice treated with angiotensin II.Physiological reports · 2022Article
- Mural Cell SRF Controls Pericyte Migration, Vessel Patterning and Blood Flow.Circulation research · 2022Article
- Age and Blood Pressure Contribute to Aortic Cell and Tissue Stiffness Through Distinct Mechanisms.Hypertension (Dallas, Tex. : 1979) · 2022Article
- Long-Term Strenuous Exercise Promotes Vascular Injury by Selectively Damaging the Tunica Media: Experimental Evidence.JACC. Basic to translational science · 2022Article
- Activin B-activated Cdc42 signaling plays a key role in regulating adipose-derived mesenchymal stem cells-mediated skin wound healing.Stem cell research & therapy · 2022Article
- SRF: a seriously responsible factor in cardiac development and disease.Journal of biomedical science · 2022Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsIncreased aortic stiffness is a fundamental manifestation of hypertension. However, the molecular mechanisms involved remain largely unknown. We tested the hypothesis that abnormal intrinsic vascular smooth muscle cell (VSMC) mechanical properties in large arteries, but not in distal arteries, contribute to the pathogenesis of aortic stiffening in hypertension, mediated by the serum response factor (SRF)/myocardin signalling pathway. METHODS AND
resultsFour month old male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were studied. Using atomic force microscopy, significant VSMC stiffening was observed in the large conducting aorta compared with the distal arteries in SHR (P < 0.001), however, this regional variation was not observed in WKY rats (P > 0.4). The increase of VSMC stiffness was accompanied by a parallel increase in the expression of SRF by 9.8-fold and of myocardin by 10.5-fold in thoracic aortic VSMCs from SHR vs. WKY rats, resulting in a significant increase of downstream stiffness-associated genes (all, P < 0.01 vs. WKY). Inhibition of SRF/myocardin expression selectively attenuated aortic VSMC stiffening, and normalized downstream targets in VSMCs isolated from SHR but not from WKY rats. In vivo, 2 weeks of treatment with SRF/myocardin inhibitor delivered by subcutaneous osmotic minipump significantly reduced aortic stiffness and then blood pressure in SHR but not in WKY rats, although concomitant changes in aortic wall remodelling were not detected during this time frame.
conclusionsSRF/myocardin pathway acts as a pivotal mediator of aortic VSMC mechanical properties and plays a central role in the pathological aortic stiffening in hypertension. Attenuation of aortic VSMC stiffening by pharmacological inhibition of SRF/myocardin signalling presents a novel therapeutic strategy for the treatment of hypertension by targeting the cellular contributors to aortic stiffness.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.