Purpose Chronic diabetes is associated with cardiovascular functional disturbances as evidenced from impaired cardiac dysfunctions. Diabetic cardiomyopathy (DCM) is one of the functional parameters and increased fibrosis. There was a sig- serious cardiovascular complications associated with diabetes. nificant increase in PAR expression after 20 weeks of diabetes Despite significant efforts in understanding the pathophysiol- induction. Four weeks argatroban treatment ameliorated met- ogy of DCM, management of DCM is not adequate due to its abolic alterations (reduced plasma glucose and cholesterol), complex pathophysiology. Recently, involvement of protease- ventricular dysfunctions (improved systolic and diastolic activated receptors (PARs) has been postulated in cardiovas- functions), cardiac fibrosis (reduced percentage area of colla- cular diseases. These receptors are activated by thrombin, gen in picro-sirius red staining), and apoptosis (reduced trypsin, or other serine proteases. Expression of PAR has been TUNEL positive nuclei). Reduced expression of PAR1 and shown to be increased in cardiac diseases such as myocardial PAR4 in the argatroban-treated group indicates a response infarction, viral myocarditis, and pulmonary arterial hyperten- towards inhibition of thrombin. In addition, AKT (Ser-473), sion. However, the role of PAR in DCM has not been eluci- GSK-3β (Ser-9), p-65 NFĸB phosphorylation, TGF-β,COX- dated yet. Therefore, in the present
Cardiovascular Drugs and Therapy – Springer Journals
Published: Jul 10, 2017
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