Heart Failure as a Comorbidity of Diabetes: Role of Dipeptidyl Peptidase 4

Abstract

Heart failure is a primary cause of death worldwide, and it is notable that heart failure patients exhibit a high incidence of diabetes. On the other hand, comorbid diabetes significantly worsens the prognosis of heart failure, even independently of complicated coronary artery disease.To date, heart failure caused by diabetes has been designated as "diabetic cardiomyopathy (DMC)," and a recent cohort study of the large-scale (1.9 million people) research platform of linked electronic medical records in UK (CALIBER registry) demonstrated that heart failure and peripheral arterial disease are the most common initial manifestations of cardiovascular disease in type 2 diabetes. The underlying pathophysiology has been characterized as microvasculopathy, myocardial hypertrophy, and cardiac fibrosis; however, these evidences are mostly obtained under a preclinical setting, and its clinical application on DMC in terms of its diagnosis and therapeutic intervention yet has reached practical. Our group has focused on and clarified the molecular mechanisms underlying DMC both in preclinical and clinical settings and has found the primary role of "dipeptidyl peptidase-4 (DPP4)" in the pathogenesis of diabetic microvasculopathy in the heart. Moreover, there are evidences implicating the potent role of circulating DPP4 activity in the diagnosis of diastolic heart failure. The present review aimed to review the current comprehension regarding diabetes and heart failure and discuss the therapeutic and diagnostic roles of DPP4. J Atheroscler

SDF‐1α (Stromal Cell‐Derived Factor 1α) Induces Cardiac Fibroblasts, Renal Microvascular Smooth Muscle Cells, and Glomerular Mesangial Cells to Proliferate, Cause Hypertrophy, and Produce Collagen

“…As recently reviewed, evidence shows that in animal models, DPP4 inhibitors have antifibrotic effects in the heart and kidneys. As recently reviewed by Fadini et al, however, the reality is that the putative cardiorenal protective effects of DPP4 inhibitors detected in some preclinical models have not been borne out in large randomized clinical trials, observational studies, or meta‐analyses.…”

Transcriptomic alterations in the heart of non-obese type 2 diabetic Goto-Kakizaki rats

“…The cleaved dipeptides are bioactive molecules regulating the cardiovascular system as well. Dpp4 inhibitors have been reported to be cardioprotective in most of the preclinical and clinical studies in T2DM [ 73 ]. In contrast, some cardiovascular outcome studies revealed increased hospitalization rates for heart failure among a subset of DPP4 inhibitor-treated diabetic subjects [ 74 ].…”

Role of microRNA in diabetic cardiomyopathy: From mechanism to intervention

“…An important pathophysiological mechanisms in progression to heart failure in diabetes is the increased risk of hypertension, which leads to increased afterload and pressure overload, eventually volume overload [25]. Interestingly, dipeptidyl peptidase-4 (DPP4), a key enzyme that regulates glucose metabolism has been reported as a potential biomarker in the diagnosis of diastolic heart failure in the patients of diabetic cardiomyopathy, further substantiating the pivotal role of glucose dysregulation in diabetic cardiomyopathy [27]. …”