Abstract
BackgroundLeft ventricle (LV) and right ventricle (RV) are characterized by well-known physiological differences, mainly related to their different embryological origin, hemodynamic environment, function, structure, and cellular composition. Nevertheless, scarce information is available about cellular peculiarities between left and right ventricular chambers in physiological and pathological contexts. Cardiac mesenchymal stromal cells (C-MSC) are key cells affecting many functions of the heart. Differential features that distinguish LV from RV C-MSC are still underappreciated.AimTo analyze the physiological differential amount, function, and transcriptome of human C-MSC in LV versus (vs.) RV.MethodsHuman cardiac specimens of LV and RV from healthy donors were used for tissue analysis of C-MSC number, and for C-MSC isolation. Paired LV and RV C-MSC were compared as for surface marker expression, cell proliferation/death ratio, migration, differentiation capabilities, and transcriptome profile.ResultsHistological analysis showed a greater percentage of C-MSC in RV vs. LV tissue. Moreover, a higher C-MSC amount was obtained from RV than from LV after isolation procedures. LV and RV C-MSC are characterized by a similar proportion of surface markers. Functional studies revealed comparable cell growth curves in cells from both ventricles. Conversely, LV C-MSC displayed a higher apoptosis rate and RV C-MSC were characterized by a higher migration speed and collagen deposition. Consistently, transcriptome analysis showed that genes related to apoptosis regulation or extracellular matrix organization and integrins were over-expressed in LV and RV, respectively. Besides, we revealed additional pathways specifically associated with LV or RV C-MSC, including energy metabolism, inflammatory response, cardiac conduction, and pluripotency.ConclusionTaken together, these results contribute to the functional characterization of RV and LV C-MSC in physiological conditions. This information suggests a possible differential role of the stromal compartment in chamber-specific pathologic scenarios.
Highlights
Left and right cardiac chambers retain well-known physiological differences, linked to their diverse embryological origin, hemodynamic environment, function, structure, and cellular composition (Friedberg and Redington, 2014; Penny and Redington, 2016). cardiomyocytes occupy 75% of adult normal myocardial tissue volume, they represent 30–40% of cardiac cells only
We proceeded with a quantitative evaluation of Cardiac mesenchymal stromal cells (C-MSC) isolated from Left ventricle (LV) and right ventricle (RV) tissues through the digestion procedure, already described in Pilato et al (2018)
For all the surface markers screened, we found a similar pattern of expression in LV and RV C-MSC, indicating no differences in the mesenchymal identity of the two populations
Summary
Left and right cardiac chambers retain well-known physiological differences, linked to their diverse embryological origin, hemodynamic environment, function, structure, and cellular composition (Friedberg and Redington, 2014; Penny and Redington, 2016). cardiomyocytes occupy 75% of adult normal myocardial tissue volume, they represent 30–40% of cardiac cells only. Left and right cardiac chambers retain well-known physiological differences, linked to their diverse embryological origin, hemodynamic environment, function, structure, and cellular composition (Friedberg and Redington, 2014; Penny and Redington, 2016). The remaining cells are non-myocytes, including smooth muscle cells, endothelial cells, fibroblasts, and mesenchymal stromal cells (Camelliti et al, 2005; Gray et al, 2018; Perbellini et al, 2018). The distribution of these cell populations in the heart is not homogeneous: the myocardium exhibits distinct regional differences that influence heart physiology and disease development (Souders et al, 2009; Pinto et al, 2016). Differential features that distinguish LV from RV C-MSC are still underappreciated
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