Up‐regulation of nestin in the infarcted myocardium potentially indicates differentiation of resident cardiac stem cells into various lineages including cardiomyocytes

Abstract

To identify proteins involved in cardiac regeneration, a proteomics approach was applied. A total of 26 proteins, which displayed aberrant expression in mouse hearts infarcted through ligation of the left anterior descending coronary artery, were identified. These included the intermediate filament protein nestin, which was up-regulated in the infarct border zone. Corresponding changes were observed for its mRNA. Nestin mRNA was also up-regulated in hearts from 17 of 19 patients with end-stage heart failure, including 4 with acute myocardial infarction in comparison with 8 donor hearts. Immunofluorescence confocal laser scanning microscopy revealed that nestin is expressed, on the one hand, in small proportions of cardiomyocytes, endothelial cells, smooth muscle cells, neuronal cells, and fibroblasts. On the other hand, it was found to be coexpressed with the stem cell markers c-kit, Sca-1, Mdr-1, and Abcg2 in small interstitial cells. In infarcted hearts from chimeric mice transplanted with bone marrow from enhanced green fluorescent protein (EGFP) transgenic mice, less than 1% of nestin-positive cells coexpressed EGFP, although EGFP-positive cells were abundant in these. Consequently, enhanced expression of nestin in the injured myocardium might reflect spontaneous regenerative processes supposedly based on the differentiation of resident cardiac stem cells into diverse cardiac cell types.

Mesenchymal Stem Cell Therapy Protects Lungs from Radiation-Induced Endothelial Cell Loss by Restoring Superoxide Dismutase 1 Expression

“…Interestingly, increasing amounts of GFP were detected in fibrotic lungs of NestGFP mice after WTI and in Nest wtBM chimeras after TBI, although an induction of resident MSCs differentiation would firstly suggest a downregulation of MSC marker proteins (namely Nestin) and thus of GFP. In line with our findings, immunofluorescence microscopy already revealed that Nestin is expressed in small proportions of fibroblasts (70). Furthermore, a concomitant appearance of Nestin-and CD34-positive myofibroblasts was observed under fibrosing conditions, suggesting that the differential expression of Nestin may not only indicate phenotypic and functional heterogeneity but may also indicate that Nestinpositive myofibroblast may represent a relatively immature subpopulation of cells with multipotentiality (41).…”

Variants in the Nestin Gene and Coronary Heart Disease

“…When studying cardiac regeneration in the mouse heart, Scobioala et al found that the expression of nestin protein was increased in the infarcted area (in cardiomyocytes, endothelial cells and smooth muscle cells) and was also co-expressed with other stem cell markers in small interstitial cells. 10 They also reported increased levels of nestin mRNA in cardiac tissue from patients with heart failure and myocardial infarction when compared with controls.…”

“…8,9 More recently, it has been recognized that nestin may play an important role in stem cells and tissue regeneration. 10 However, there is limited evidence concerning its function in the human heart. When studying cardiac regeneration in the mouse heart, Scobioala et al found that the expression of nestin protein was increased in the infarcted area (in cardiomyocytes, endothelial cells and smooth muscle cells) and was also co-expressed with other stem cell markers in small interstitial cells.…”

Nestin upregulation characterizes vascular remodeling secondary to hypertension in the rat

“…Despite the plethora of data supporting the premise that nestin expression identified a stem cell phenotype, recent studies have detected the intermediate filament protein in numerous non-stem cell populations during physiological growth and pathological remodeling. Nestin was highly expressed in developing skeletal myofibers and downregulated following maturation, upregulated in endothelial cells during reparative angiogenesis, and induced in mesangial cells following injury and in scar myofibroblasts and cardiac myocyte-like cells bordering the peri-infarct/infarct region of the ischemically damaged rodent and human heart (1,3,4,7,9,11,24,25,31,32). However, in contrast to neural progenitor/stem cells, expression of the intermediate filament protein in skeletal myofibers and endothelial cells was driven by the first intron of the nestin gene (1,42,43).…”