Calcium is a highly positively charged ionic species. It regulates all cell types’ functions and is an important second messenger that controls and triggers several mechanisms, including membrane stabilization, permeability, contraction, secretion, mitosis, intercellular communications, and in the activation of kinases and gene expression. Therefore, controlling calcium transport and its intracellular homeostasis in physiology leads to the healthy functioning of the biological system. However, abnormal extracellular and intracellular calcium homeostasis leads to cardiovascular, skeletal, immune, secretory diseases, and cancer. Therefore, the pharmacological control of calcium influx directly via calcium channels and exchangers and its outflow via calcium pumps and uptake by the ER/SR are crucial in treating calcium transport remodeling in pathology. Here, we mainly focused on selective calcium transporters and blockers in the cardiovascular system.

The vascular endothelium plays a vital role during embryogenesis and aging and is a cell monolayer that lines the blood vessels. The immune system recognizes the endothelium as its own. Therefore, an abnormality of the endothelium exposes the tissues to the immune system and provokes inflammation and vascular diseases such as atherosclerosis. Its secretory role allows it to release vasoconstrictors and vasorelaxants as well as cardio-modulatory factors that maintain the proper functioning of the circulatory system. The sealing of the monolayer provided by adhesion molecules plays an important role in cardiovascular physiology and pathology.

The 3-dimensional confocal microscopy technique has allowed us to identify the presence of yet another cardioactive factor and its receptor, namely neuropeptide Y (NPY) and its Y₁receptor, at the level of vascular smooth muscle cells and heart cells including endocardial endothelial cells (EECs). Using this technique, we also demonstrated that NPY is able to induce an increase in both cytosolic and nuclear calcium in all these cell types. Furthermore, besides being expressed at the level of EECs, NPY is also released from these cells following a sustained increase of intracellular Ca²⁺. This suggests the ability of NPY to contribute to the regulation of the excitation–secretion coupling of EECs and the excitation–contraction coupling of cardiomyocytes and vascular smooth muscle cells.

He aims of the present study are to investigate the presence and distribution of angiotensin II (Ang II), as well as AT₁and AT₂receptors, in endocardial endothelial cells (EECs) and to determine if the effect of Ang II on intracellular calcium in these cells is mediated via the AT₁or the AT₂receptor. Immunofluorescence and 3D confocal microscopy techniques were used on 20-week-old fetal human EECs. Our results showed that Ang II and its receptors, the AT₁and the AT₂types, are present and exhibit a different distribution in human EECs. Ang II labelling is found throughout the cell with a fluorescence signal higher in the cytosol when compared with the nucleus. Like Ang II, the AT₁receptor fluorescence signal is also homogeneously distributed in human EECs but with a preferential labelling at the level of the nucleus, while the AT₂receptor labelling is solely present in the nucleus. Using fluo-3 and 3D confocal microscopy technique, superfusion of human EECs with increasing concentration of Ang II induced a dose-dependent sustained increase in free cytosolic and nuclear Ca²⁺levels. This effect of Ang II on human EEC's intra cellular Ca²⁺([Ca²⁺]_i) was completely prevented by losartan, an AT₁receptor antagonist. Our results suggest that Ang II, as well as AT₁and AT₂receptors, is present but differentially distributed in EECs of 20-week-old fetal human hearts, and that the AT₁receptor mediates the effects of Ang II on [Ca²⁺]_iin these cells.Key words: angiotensin II, nuclear receptors, endocardial endothelial cells, Ang II receptors, intracellular calcium.

Hyperinsulinemia refers to an elevated level of circulating insulin (80 and 100 µU/mL), often leading to metabolic disorders such as obesity, insulin resistance, and type 2 diabetes (T2D). There is no precise and universally accepted definition of hyperinsulinemia and insulin resistance. The literature in the field remains unclear regarding whether insulin resistance precedes the development of hyperinsulinemia. Recently, a new hypothesis has been proposed suggesting that chronic hyperinsulinemia precedes and causes insulin resistance. The causes of the initiation of hyperinsulinemia, insulin resistance, and type 2 diabetes are multifactorial. Thus, it is not easy to define in general. Recent work demonstrates that the main prediabetic factor leading to insulin resistance is chronic hyperinsulinemia. However, recent work in the literature proposes that relatively long-term hyperinsulinemia does precede insulin resistance and already promotes cardiovascular remodeling. This later may lead to the development of vascular diseases such as hypertension. Thus, defining hyperinsulinemia and insulin resistance, as well as their signaling pathways implicated in the development of type 2 diabetes (T2D), needs to be clarified.