scholarly journals Angiocrine FSTL1 insufficiency leads to atrial and vein wall fibrosis via SMAD3 activation

2019 ◽  
Author(s):  
Haijuan Jiang ◽  
Luqing Zhang ◽  
Xuelian Liu ◽  
Wei Sun ◽  
Katsuhiro Kato ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Heart Valves ◽  
Smooth Muscle Actin ◽  
Vascular Wall ◽  
Cell Interaction ◽  
Alpha Smooth Muscle Actin ◽  
Vein Wall ◽  
Mural Cell ◽  
Smad3 Phosphorylation ◽  
Cardiovascular Fibrosis

AbstractAngiocrine factors, mediating the endothelial-mural cell interaction in vascular wall construction as well as maintenance, are incompletely characterized. Here we show that loss of follistatin-like protein 1 (FSTL1) in endothelial cells (Fstl1ECKO) led to an increase of pulmonary vascular resistance, resulting in the heart regurgitation especially with tricuspid valves. However, this abnormality was not detected in mutant mice with Fstl1 deletion in smooth muscle cells or hematopoietic cells. We further showed that there was excessive alpha-smooth muscle actin (αSMA) associated with atrial endocardia, heart valves, veins and microvessels after the endothelial FSTL1 deletion. Consistently, there was an increase of collagen deposition as demonstrated in livers of Fstl1ECKO mutants. The SMAD3 phosphorylation was significantly enhanced and pSMAD3 staining was colocalized with αSMA in vein walls, suggesting the activation of TGFβ signaling in vascular mural cells of Fstl1ECKO mice. The findings imply that endothelial FSTL1 is critical for the homeostasis of atria and veins and its insufficiency may favor cardiovascular fibrosis leading to heart failure.

scholarly journals Placental vascular remodeling in pregnant women with COVID-19

2021 ◽  
Author(s):  
Sergiy G. Gychka ◽  
Iurii L. Kuchyn ◽  
Tetyana V. Savchuk ◽  
Sofia I. Nikolaienko ◽  
Volodymyr M. Zhezhera ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Remodeling ◽  
Smooth Muscle Actin ◽  
Fold Increase ◽  
Vascular Wall ◽  
Host Cells ◽  
Wall Thickening ◽  
Alpha Smooth Muscle Actin ◽  
Angiotensin Converting Enzyme 2 ◽  
Smooth Muscle Proliferation

Severe acute respiratory syndrome coronavirus 2 has been causing the pandemic of coronavirus disease 2019 (COVID-19) that has so far resulted in over 180 million infections and nearly 4 million deaths. This respiratory virus uses angiotensin-converting enzyme 2 as a receptor to enter host cells, exhibiting a unique feature that affects various tissues in addition to the lungs. The present study reports that the placental arteries from women who gave birth to live full-term newborns while developing of COVID-19 during pregnancy exhibit severe vascular wall thickening and the occlusion of the vascular lumen. A morphometric analysis of the placental arteries stained with hematoxylin and eosin suggest a 2-fold increase in wall thickness and a 5-fold decrease in the lumen area. Immunohistochemistry with alpha-smooth muscle actin and Masson's trichrome staining showed that such placental vascular remodeling in COVID-19 is associated with smooth muscle proliferation and fibrosis. Placental vascular remodeling may represent a mechanism of the clinical problems associated with childbirth in COVID-19 patients.

Abstract 724: Synectin is Required for Normal PDGF Secretion and Smooth Muscle Cell Basic Science Recruitment

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Julie M Paye ◽  
Thomas W Chittenden ◽  
Li-Kun Phng ◽  
Holger Gerhardt ◽  
Michael Simons
Keyword(s):  
Endothelial Cells ◽  
Transcriptional Regulation ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Smooth Muscle Actin ◽  
Alpha Smooth Muscle Actin ◽  
Arterial Tree ◽  
Mural Cell ◽  
Post Transcriptional Regulation

Background: Synectin, a ubiquitously expressed scaffold and PDZ protein, has been shown to be a key regulator in the formation of arterial vasculature. Primary arterial endothelial cells isolated from synectin−/− mice exhibited defects in PDGF signaling that were not present in arterial synectin+/+ or either venous synectin+/+ or synectin−/− endothelial cells. Methods: To address the role of synectin in mural cell recruitment, retinas from synectin−/− (KO) and synectin+/+ (WT) mice were stained for isolectin and alpha-smooth muscle actin. To determine the mechanisms responsible for defective smooth muscle cells recruitment, primary arterial and venous endothelial (EC) and smooth muscle (SMC) cells were isolated from synectin+/+ and synectin−/− mice. Results: Examination of the retinal vasculature in synectin−/− mice demonstrated poor smooth muscle cell coverage of the forming arterial tree with a number of SMC cells sitting some distance away from the vessels, a defect reminiscent of retinal abnormalities observed in PDGF-B−/− mice. Western blot analysis of lysates from primary KO SMC demonstrated levels of PDGFR-β analogous to WT, although expression of PDGF-B was markedly reduced in lysates from arterial, but not venous, primary KO endothelial cells. Transduction of KO EC with an adenoviral synectin construct was sufficient to restore PDGF-B protein levels. Further, qPCR was used to determine whether defects in PDGF-B protein production were at the transcription or translation level. Interestingly, there was only a minor decrease in the amount of PDGF-B mRNA in KO compared to WT EC, suggesting that synectin deficiency has selectively affected post-transcriptional regulation of PDGF-B expression. Migration of WT and KO SMC in response to PDGF-B or conditioned media from WT and KO endothelial cells was also assessed to determine the cell type specificity of PDGF defects in KO mice. Conclusions: Synectin is required for post-transcriptional regulation of PDGF-B in endothelial cells. Deficits in PDGF-B secretion by synectin−/− endothelial cells result in inadequate smooth muscle recruitment and coverage of arterial vessels.

scholarly journals 20-HETE-promoted cerebral blow flow autoregulation is associated with enhanced α-smooth muscle actin positive cerebrovascular pericyte contractility

2021 ◽  
Author(s):  
Yedan Liu ◽  
Huawei Zhang ◽  
Tina Yu ◽  
Xing Fang ◽  
Jane J. Ryu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Essential Role ◽  
Smooth Muscle Actin ◽  
Dienoic Acid ◽  
Muscle Actin ◽  
Alpha Smooth Muscle Actin ◽  
Synthesis Inhibitor ◽  
Mural Cell ◽  
Cell Contractility ◽  
Sd Rats

ABSTRACTWe previously reported that deficiency in 20-HETE or CYP4A impaired the myogenic response and autoregulation of cerebral blood flow (CBF) in rats. The present study demonstrated that CYP4A was coexpressed with alpha-smooth muscle actin (α-SMA) in vascular smooth muscle cells (VSMCs) and most pericytes along parenchymal arteries (PAs) isolated from SD rats. Cell contractile capabilities of cerebral VSMCs and pericytes were reduced with a 20-HETE synthesis inhibitor, N-Hydroxy-N′-(4-butyl-2-methylphenyl)-formamidine (HET0016) but restored with 20-HETE analog 20-hydroxyeicosa-5(Z),14(Z)-dienoic acid (WIT003). Similarly, intact myogenic responses of the middle cerebral artery and PA of SD rats decreased with HET0016 and rescued by WIT003. Lastly, HET0016 impaired well autoregulated CBF in the surface and deep cortex of SD rats. These results demonstrate that 20-HETE has a direct effect on cerebral mural cell contractility that may play an essential role in CBF autoregulation.

Expression of alpha-smooth muscle actin, TGF-β1 and TGF-β type II receptor during connective tissue contraction

1997 ◽  
Vol 33 (8) ◽  
pp. 622-627 ◽  
Author(s):  
M. Reza Ghassemifar ◽  
Roy W. Tarnuzzer ◽  
Nasser Chegini ◽  
Erkki Tarpila ◽  
Gregory S. Schultz ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Connective Tissue ◽  
Smooth Muscle Actin ◽  
Type Ii ◽  
Muscle Actin ◽  
Alpha Smooth Muscle Actin ◽  
Tissue Contraction ◽  
Tgf Β1
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