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Canagliflozin Inhibits Human Endothelial Cell Proliferation and Tube Formation
In conclusion, the present study identified canagliflozin as a potent inhibitor of human EC proliferation. The anti-proliferative action of canagliflozin is observed in ECs isolated from both the venous and arterial circulation, and is partly due to the blockade of cyclin A expression. In addition, this study found that canagliflozin inhibits tube formation in cultured ECs and mouse aortic rings. Notably, these actions are specific for canagliflozin and not seen with other SGLT2 inhibitors. The ability of canagliflozin to exert these pleiotropic effects on EC function may contribute to both the adverse and salutary actions...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

Impact of CHA2DS2VASc Score on Candidacy for Anticoagulation in Patients With Atrial Fibrillation: A Multipayer Analysis.
Abstract PURPOSE: The purpose of this study is to report on the effect of using CHA2DS2VASc (congestive heart failure, hypertension, age ≥75 years [doubled], type 1 or type 2 diabetes mellitus, stroke or transient ischemic attack or thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]) rather than CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke) to determine candidacy for anticoagulant prophylaxis in insured patients with atrial fibrillation (AF). MET...
Source: Clinical Therapeutics - September 22, 2016 Category: Drugs & Pharmacology Authors: Patel AA, Nelson WW, Schein J Tags: Clin Ther Source Type: research

Long-term administration of angiotensin (1–7) prevents heart and lung dysfunction in a mouse model of type 2 diabetes (db/db) by reducing oxidative stress, inflammation and pathological remodeling.
In this study, 8 week-old db/db mice were administered A[1–7] daily via subcutaneous injections. After 16 weeks of treatment, echocardiographic assessment of heart function demonstrated significant improvement in cardiac output, stroke volume and shortening fraction in diabetic animals. A[1–7] also prevented cardiomyocyte hypertrophy, apoptosis, lipid accumulation, and decreased diabetes-induced fibrosis and OS in the heart tissue. Treatment with A[1–7] reduced levels of circulating proinflammatory cytokines that contribute to the low grade inflammation observed in diabetes. In addition, lung pathologies associated w...
Source: Pharmacological Research - March 6, 2016 Category: Drugs & Pharmacology Source Type: research

Diabetes and Complications: Cellular Signalling Pathways, Current Understanding and Targeted Therapies.
Abstract Diabetes is a metabolic disorder and over the past decades, it has become a major cause for morbidity and mortality affecting the youth and middle-aged as it is fourth leading cause of disease related to death. In both type 1 and type 2 diabetes the severe pathogenesis causes micro vascular complications: nephropathy, retinopathy, neuropathyand macro vascular complications:cardiovascular disease, heart attacks and stroke.Under hyperglycemia, activation of different signalling mechanisms such as increased polyol pathway, advanced-glycation end product formation, activation of Protein Kinase C and hexosamin...
Source: Current Drug Targets - December 9, 2015 Category: Drugs & Pharmacology Authors: Adeshara KA, Diwan AG, Tupe RS Tags: Curr Drug Targets Source Type: research

Cardiovascular effects of current and future anti-obesity drugs.
Abstract The prevalence of obesity increases and is associated with increases in co-morbidities e.g. type 2 diabetes, hyperlipidemia, hypertension, obstructive sleep apnea, heart disease, stroke, asthma, several forms of cancer, depression, and may result in reduction of expected remaining lifespan. We have reviewed the adverse effects on the cardiovascular system of anti-obesity drugs now retracted from the market as well as the cardiovascular profile of current drugs and potential pathways which are considered for treatment of obesity. Fenfluramine, and sibutramine were withdrawn due to increased cardiovascular ...
Source: Current Vascular Pharmacology - May 24, 2014 Category: Drugs & Pharmacology Authors: Comerma-Steffensen S, Grann M, Andersen CU, Rungby J, Simonsen U Tags: Curr Vasc Pharmacol Source Type: research