Mechanisms of Regenerative Potential Activation in Cardiac Mesenchymal Cells

Abstract

Recovery of the contractile function of the heart and the regeneration of the myocardium after ischemic injury are contemporary issues in regenerative medicine and cell biology. This study aimed to analyze early transcriptional events in cardiac tissue after infarction and to explore the cell population that can be isolated from myocardial tissue. We induced myocardial infarction in Wistar rats by permanent ligation of the left coronary artery and showed a change in the expression pattern of Notch-associated genes and Bmp2/Runx2 in post-MI tissues using RNA sequencing and RT-PCR. We obtained primary cardiac mesenchymal cell (CMC) cultures from postinfarction myocardium by enzymatic dissociation of tissues, which retained part of the activation stimulus and had a pronounced proliferative potential, assessed using a “xCELLigence” real-time system. Hypoxia in vitro also causes healthy CMCs to overexpress Notch-associated genes and Bmp2/Runx2. Exogenous activation of the Notch signaling pathway by lentiviral transduction of healthy CMCs resulted in a dose-dependent activation of the Runx2 transcription factor but did not affect the activity of the Bmp2 factor. Thus, the results of this study showed that acute hypoxic stress could cause short-term activation of the embryonic signaling pathways Notch and Bmp in CMCs, and this interaction is closely related to the processes of early myocardial remodeling after a heart attack. The ability to correctly modulate and control the corresponding signals in the heart can help increase the regenerative capacity of the myocardium before the formation of fibrotic conditions.

A myocardial infarct border-zone-on-a-chip demonstrates distinct regulation of cardiac tissue function by an oxygen gradient

“…To measure the similarity of our model to adult myocardial tissue after acute MI, we compared our transcriptomic data to that of adult myocardium of rats 24 hours after MI caused by surgical ligation and healthy myocardium of sham-operated rats as controls ( 55 ). Compared with rat MI transcriptomic data, the DEGs ( P < 0.05) of the O 2 gradient overlapped with >2000 genes (fig.…”

Gene expression patterns and related pathways in the hearts of rhesus monkeys subjected to prolonged myocardial ischemia

“…In addition to the rhesus monkey model, several small animals, such as mice and rats, and large animals, such as dogs and pigs, have been widely used in IHD-related studies. [38][39][40] Among those transcriptomic studies, in the rat MI model (at least eight weeks after MI), the main upregulated pathways were cytoskeletal and ECM proteins. Gene expression levels of NPPA, NPPB, collagen III, biglycan, fibronectin, biglycan, THBS4, lysyl oxidase, and complement factor B were significantly upregulated, and contractile genes were downregulated.…”

Calciprotein Particles Induce Cellular Compartment-Specific Proteome Alterations in Human Arterial Endothelial Cells

“…Such conditioned medium does not include CPPs but is enriched with pro-inflammatory cytokines (i.e., interleukin-6, interleukin-8, and monocyte chemoattractant protein 1) that might activate the intact ECs, thus inducing endothelial activation and mimicking the paracrine effects of CPP internalisation. In addition, the investigation of the interactome between CPP-treated ECs and intact vascular smooth muscle cells is a promising research direction in light of the recent discoveries on EC-guided, context-specific mesenchymal cell differentiation [122][123][124]. Dysfunctional ECs might indirectly promote the development of vascular or valvular calcification (as CPPs are incapable of penetrating elastic laminae which delimitate vascular smooth muscle cell layers).…”