Vascular smooth muscle remodeling in health and disease.

In blood vessels, vascular smooth muscle cells (VSMCs) generally exist in two major phenotypes: contractile and non-contractile (synthetic). The contractile phenotype is predominant and includes quiescent or differentiated VSMCs, which function as the regulators of blood vessel diameter and blood flow. According to some literature in the field, contractile VSMCs do not switch to the non-contractile phenotype due to the activation of specific transcription factors that are considered as guardians of the contractile phenotype. However, a vast amount of the literature uses the terms remodeling and phenotype switching of contractile VSMCs interchangeably based mainly on studies dealing with atherosclerosis. The use of the terms remodeling and switching to describe changes in phenotype based on morphological criteria can be confusing. The term remodeling was first used to describe morphological changes in the heart and was soon used to describe phenotype changes of contractile VSMCs based on morphological criteria. The latter were introduced in early studies, and new molecular criteria were later added, including changes in gene expression, which could be irreversible. In this review, we will discuss the different views concerning remodeling and possible switching of contractile VSMCs to a non-contractile phenotype. We conclude that only remodeling of contractile VSMCs may take place upon vascular injury and disease.

Angiotensin II induces apoptosis of human right and left ventricular endocardial endothelial cells by activating the AT2 receptor 1.

Endocardial endothelial cells (EECs) form a monolayer lining the ventricular cavities. Studies from our laboratory and the literature have shown differences between EECs isolated from the right and left ventricles (EECRs and EECLs, respectively). Angiotensin II (Ang II) was shown to induce apoptosis of different cell types mainly via AT1 receptor activation. In this study, we verified whether Ang II induces apoptosis of human EECRs and EECLs (hEECRs and hEECLs, respectively) and via which type of receptor. Using the annexin V labeling and in situ TUNEL assays, our results showed that Ang II induced apoptosis of both hEECRs and hEECLs in a concentration-dependent manner. Our results using specific AT1 and AT2 receptor antagonists showed that the Ang-II-induced apoptosis in both hEECRs and hEECLs is mediated mainly via the AT2 receptor. However, AT1 receptor blockade partially prevented Ang-II-induced apoptosis, particularly in hEECRs. Hence, our results suggest that mainly AT2 receptors mediate Ang-II-induced apoptosis of hEECRs and hEECLs. The damage of EECs would affect their function as a physical barrier between the blood and cardiomyocytes, thus affecting cardiomyocyte functions.

Difference in the response to angiotensin II between left and right ventricular endocardial endothelial cells.

Previous studies focused on the right ventricular endocardial endothelial cells (EECRs) and showed that angiotensin II (Ang II) induced increase in cytosolic and nuclear calcium via AT1 receptor activation. In the present study, we verified whether the response of left EECs (EECLs) to Ang II is different than that of EECRs. Our results showed that the EC50 of the Ang II-induced increase of cytosolic and nuclear calcium in EECLs was 10× higher (around 2 × 10-13 mol/L) than in EECRs (around 8 × 10-12 mol/L). The densities of both AT1 and AT2 receptors were also higher in EECLs than those previously reported in EECRs. The effect of Ang II was mediated in both cell types via the activation of AT1 receptors. Treatment with Ang II induced a significant increase of cytosolic and nuclear AT1 receptors in EECRs, whereas the opposite was found in EECLs. In both cell types, there was a transient increase of cytosolic and nuclear AT2 receptors following the Ang II treatment. In conclusion, our results showed that both AT1 and AT2 receptors densities are higher in both EECLs compared to what was reported in EECRs. The higher density of AT1 receptors in EECLs compared to REECs may explain, in part, the higher sensitivity of EECLs to Ang II.