Immunophilins and cardiovascular complications.

Immunophilins belong to a highly conserved family of proteins with cis-trans peptidyl-prolyl isomerase activity, generally classified by their ability to selectively bind specific immunosuppressive drugs, thereby regulating their activity. Immunophilins include Cyclophilins (CyPs), which are specific targets of the immunosuppressant drug cyclosporin A (CsA); FKBPs (FK506-binding proteins), that are sensitive to both FK506 (tacrolimus) and rapamycin (sirolimus); and FCBPs which are sensitive to CsA and FK506. Immunophilins are expressed in multiple human tissues, including brain, heart, kidney, liver and lung and regulate functions as diverse as intracellular calcium signaling, protein transport, protein folding and gene transcription. In particular, immunophilins play key functional roles in the cardiovascular system, where they can associate with proteins such as ryanodine and IP3 receptors (RyR and IP3R), calcineurin, and mitochondrial permeability transition pore (MPTP) and Heat-shock proteins-caveolin-cholesterol complex and regulate their function. The biological importance of immunophilins is further revealed by the pathophysiology, as they have been implicated in several cardiovascular diseases, including vascular stenosis, atherosclerosis, heart failure and arrhythmias. This review summarizes some of the most recent studies on immunophilins and focuses on their roles in the mechanisms underlying the cardiovascular disease.

Study of the reversibility of endothelial dysfunction in a rat model of diabetes mellitus: experimental treatment by transplantation of pancreatic islets.

OBJECTIVE: To study the endothelial dysfunction induced in a rat model of diabetes mellitus, and to find out if transplantation of islet cells is an effective treatment for the endothelial damage. DESIGN: Experimental study. SETTING: University hospital, Spain. ANIMALS: 24 Wistar rats in 3 groups of each: control, diabetic and transplanted. INTERVENTIONS: Diabetes was induced in the diabetic and transplanted animals by intravenous injection of streptozocin 45 mg/Kg. In the transplanted group fresh pancreatic islet from syngeneic donor rats (1200-1500/receptor) were injected intraportally 16 weeks after the induction of diabetes. The rats were killed at 18 weeks. Excision of rings of thoracic aorta, which were contracted with 0(-5) M phenylephrine. Once the maximum contraction had been reached relaxation was induced with 10(-5) M acetylcholine and then 10(-4) M independent nitroprusside endothelial vasodilator was added. MAIN OUTCOME MEASURES: Blood glucose concentrations throughout the experiment. Mean vasodilator response to acetylcholine as an indicator of recovery of endothelial function. RESULTS: The mean (SD) vasodilatation in the control group differed significantly from that in the diabetic group (27.6 (3.9) g compared with 20.1 (3.9) p = 0.002). The transplanted group also differed from the diabetic group (25.8 (3.6) g, p = 0.009). There was no significant difference between the transplanted group and the control group (p = 0.33). CONCLUSION: In rats diabetes mellitus causes considerable endothelial damage, which can be reversed by transplantation of pancreatic islets.