Myocardium Of Interventricular Septum Research Articles

Proliferative Potential of Cardiomyocytes in Hypertrophic Cardiomyopathy: Correlation with Myocardial Remodeling.

Proliferating Ki-67+ cardiomyocytes were detected in the interventricular septum myocardium of adult patients with hypertrophic cardiomyopathy. In the same patients, the severity of hypertrophy and the degree of cardiomyocyte differentiation were assessed by the content of myofibrils, ultrastructural morphology, and the pattern of connexin 43-containing gap junction distribution. Adult Ki-67+ cardiomyocytes containing sarcomeric α-actin (sarc α-act+) in the sarcoplasm (diameter 23.9±6.9 μ) were detected in the myocardium of patients with hypertrophic cardiomyopathy; their relative content varied from 2 to 3084 cells per 1 million cardiomyocytes. Small early differentiating Ki-67+/sarc α-act+ cardiomyocytes with a thin cytoplasm layer (diameter 5.9±1.7 μ) constituted from 3 to 2262 cells per 1 million cardiomyocytes. These cells were found in the myocardium with the most pronounced structural changes: hypertrophy of cardiomyocytes with signs of their partial dedifferentiation.

Resident Stem Cells in the Myocardium of Patients with Obstructive Hypertrophic Cardiomyopathy

Interventricular septum myocardium was studied in 40 patients with obstructive hypertrophic cardiomyopathy. Immunohistochemical assay revealed c-kit-positive resident cardiac stem cells in 82.5% patients. The content of the connective tissue and myofibrillar disarray zones and the degree of cardiomyocyte hypertrophy and myolysis were determined. In 30% cases, cardiomyocytes containing atrial natriuretic peptide were detected in the interventricular septum myocardium. The data were compared with clinical and functional parameters of patients. It was found that cardiac stem cells are present in patients, whose myocardium was characterized by increased density of the connective tissue, hypertrophy of mature cardiomyocytes, medium degree of myolysis in them, and accumulation of natriuretic peptide, a cardiac failure marker, in cardiomyocytes.

Partial rescue of defects in Cited2-deficient embryos by HIF-1α heterozygosity

Hypoxia inducible factor-1 (HIF-1) initiates key cellular and tissue responses to physiological and pathological hypoxia. Evidence from in vitro and structural analyses supports a critical role for Cited2 in down-regulating HIF-1-mediated transcription by competing for binding with oxygen-sensitive HIF-1α to transcriptional co-activators CBP/p300. We previously detected elevated expression of HIF-1 target genes in Cited2 −/− embryonic hearts, indicating that Cited2 inhibits HIF-1 transactivation in vivo. In this study, we show for the first time that highly hypoxic cardiac regions in mouse embryos corresponded to the sites of defects in Cited2 −/− embryos and that defects of the outflow tract, interventricular septum, cardiac vasculature, and hyposplenia were largely rescued by HIF-1α haploinsufficiency. The hypoxia of the outflow tract and interventricular septum peaked at E13.5 and dissipated by E15.5 in wild-type hearts, but persisted in E15.5 Cited2 −/− hearts. The persistent hypoxia and abnormal vasculature in the myocardium of interventricular septum in E15.5 Cited2 −/− hearts were rescued with decreased HIF-1α gene dosage. Accordingly, mRNA levels of HIF-1-responsive genes were reduced in Cited2 −/− embryonic hearts by HIF-1α heterozygosity. These findings suggest that a precise level of HIF-1 transcriptional activity critical for normal development is triggered by differential hypoxia and regulated through feedback inhibition by Cited2.