Key result
Nestin protein levels were significantly upregulated in the pressure-overloaded left ventricle of rats and localized in collagen-expressing mesenchymal cells and interstitial CD31(+)- cells.
Nestin expression is upregulated in the pressure-overloaded rat heart and localizes to collagen-expressing mesenchymal cells and interstitial CD31(+) cells, highlighting a novel feature of cardiac remodeling and reactive fibrosis.
Answers are grounded in this paper and cite their sources.
Remains preclinical without human data; leaves open nestin as fibrosis mediator in pressure overload.
Renal and lung fibrosis was characterized by the accumulation of collagen-immunoreactive mesenchymal cells expressing the intermediate filament protein nestin. The present study tested the hypothesis that nestin expression was increased in the hypertrophied/fibrotic left ventricle of suprarenal abdominal aorta constricted adult male Sprague-Dawley rats and induced in ventricular fibroblasts by pro-fibrotic peptide growth factors. Nestin protein levels were upregulated in the pressure-overloaded left ventricle and expression positively correlated with the rise of mean arterial pressure. In sham and pressure-overloaded hearts, nestin immunoreactivity was detected in collagen type I(+)-and CD31(+)-cells identified in the interstitium and perivascular region whereas staining was absent in smooth muscle α-actin(+)-cells. A significantly greater number of collagen type I(+)-cells co-expressing nestin was identified in the left ventricle of pressure-overloaded rats. Moreover, an accumulation of nestin(+)-cells lacking collagen, CD31 and smooth muscle α-actin staining was selectively observed at the adventitial region of predominantly large calibre blood vessels in the hypertrophied/fibrotic left ventricle. Angiotensin II and TGF-β1 stimulation of ventricular fibroblasts increased nestin protein levels via phosphatidylinositol 3-kinase- and protein kinase C/SMAD3-dependent pathways, respectively. CD31/eNOS(+)-rat cardiac microvascular endothelial cells synthesized/secreted collagen type I, expressed prolyl 4-hydroxylase and TGF-β1 induced nestin expression. The selective accumulation of adventitial nestin(+)-cells highlighted a novel feature of large vessel remodelling in the pressure-overloaded heart and increased appearance of collagen type I/nestin(+)-cells may reflect an activated phenotype of ventricular fibroblasts. CD31/collagen/nestin(+)-interstitial cells could represent displaced endothelial cells displaying an unmasked mesenchymal phenotype, albeit contribution to the reactive fibrotic response of the pressure-overloaded heart remains unknown.
No takes yet. Share an insight, caveat, or question.
Hertig et al. (2017) studied Cardiac hypertrophy and reactive fibrosis (n=16). Suprarenal abdominal aorta constriction vs. Sham surgery was evaluated on Nestin protein expression and localization (p=<0.05). Nestin protein levels were significantly upregulated in the pressure-overloaded left ventricle of rats and localized in collagen-expressing mesenchymal cells and interstitial CD31(+)- cells.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: