The SOCE Machinery: An Unbalanced Knowledge between Left and Right Ventricular Pathophysiology

Abstract

Right ventricular failure (RVF) is the most important prognostic factor for morbidity and mortality in pulmonary arterial hypertension (PAH) or pulmonary hypertension (PH) caused by left heart diseases. However, right ventricle (RV) remodeling is understudied and not targeted by specific therapies. This can be partly explained by the lack of basic knowledge of RV remodeling. Since the physiology and hemodynamic function of the RV differ from those of the left ventricle (LV), the mechanisms of LV dysfunction cannot be generalized to that of the RV, albeit a knowledge of these being helpful to understanding RV remodeling and dysfunction. Store-operated Ca2+ entry (SOCE) has recently emerged to participate in the LV cardiomyocyte Ca2+ homeostasis and as a critical player in Ca2+ mishandling in a pathological context. In this paper, we highlight the current knowledge on the SOCE contribution to the LV and RV dysfunctions, as SOCE molecules are present in both compartments. he relative lack of studies on RV dysfunction indicates the necessity of further investigations, a significant challenge over the coming years.

Retinoic acid modulation guides human-induced pluripotent stem cell differentiation towards left or right ventricle-like cardiomyocytes

“…7A). These data are consistent with HRA-EHTs showing a more LV-like phenotype, as the LV has a stronger contractile force and higher oxygen consumption compared to RV [3,48].…”

Retinoic acid modulation guides human-induced pluripotent stem cell differentiation towards left or right ventricle-like cardiomyocytes

“…The contractile force and beating frequency in HRA-EHTs were more sensitive to hypoxia as compared to the control-EHTs, while the LRA-EHTs showed an intermediate response (Figure 7A). These data are consistent with HRA-EHTs showing a more LV-like phenotype, as the LV has a stronger contractile force and higher oxygen consumption compared to RV [3,47] β-adrenergic stimulation: The β-adrenoceptor agonist isoprenaline signi cantly increased the contractile force and beating frequency of the EHTs (Figure 7B). RT-qPCR analysis revealed high expression of the βadrenoceptor gene, ADRB1, within the HRA-EHT (Figure 7C).…”

Pulmonary Hypertension-Associated Right Ventricular Cardiomyocyte Remodelling Reduces Treprostinil Function

“…PH RV cardiomyocytes also exhibited structural changes, including sarcomere irregularity and hypertrophy, indicative of maladaptive hypertrophic remodelling [13,22,27]. The comparison of the Sarcomere Shortening and Cell Length Deflection indicated a loss of the Cell Length Deflection lusitropic effect in PH, indicating impaired RV cardiomyocyte relaxation and suggesting pathology-associated impairment in the contractile machinery or an alteration in the basal Ca 2+ load [37,38].…”