Clinical calcineurin inhibitors like Cyclosporine A and Tacrolimus paradoxically induce pathological vascular effects similar to calcineurin activators, contributing to hypertension.
This review highlights the complex and sometimes paradoxical effects of calcineurin signaling and its clinical inhibitors on vascular smooth muscle cells, emphasizing the need to balance calcineurin activity to prevent vascular pathology such as hypertension.
Calcineurin is a serine/threonine phosphatase that classically regulates T cell activation and modulates immune response by targeting transcription factors of the NFaT family. Activation of calcineurin for example by angiotensin II, phenylephrine, endothelin-1 or mechanical stress can influence vascular smooth muscle cell function and stimulates proliferation and migration or affect the phenotype of these respective cells. This can lead to vessel wall remodeling, increased vascular tone or fibrosis, which contribute to the development of cardiovascular diseases. Based on its classical function, inhibition of calcineurin activity by calcineurin inhibitors is a common treatment in the clinics for autoimmune and inflammatory disease or to prevent graft rejection. Classical calcineurin inhibitors can promote pathological effects in vasculature that resemble calcineurin activation, namely the development of systemic hypertension or inflammatory processes, making the interpretation of the role of calcineurin in vascular smooth muscle cells difficult. In this mini review, we provide a summary of known pathological outcomes of calcineurin activation and calcineurin inhibitor-induced effects in vascular smooth muscle cells. Knowledge about these functional alterations can provide a useful tool to avoid negative effects for the vasculature during pharmacological intervention. Overall, maintenance of a balanced calcineurin activity is essential for proper vascular smooth muscle cell function.
Nolze et al. (Fri,) conducted a review in Cardiovascular diseases and hypertension. Calcineurin inhibitors (Cyclosporine A, Tacrolimus) was evaluated. Clinical calcineurin inhibitors like Cyclosporine A and Tacrolimus paradoxically induce pathological vascular effects similar to calcineurin activators, contributing to hypertension.