Is there a Chance to Promote Arteriogenesis by DPP4 Inhibitors Even in Type 2 Diabetes? A Critical Review

Abstract

Cardiovascular diseases (CVD) are still the prevailing cause of death not only in industrialized countries, but even worldwide. Type 2 diabetes mellitus (type 2 DM) and hyperlipidemia, a metabolic disorder that is often associated with diabetes, are major risk factors for developing CVD. Recently, clinical trials proved the safety of gliptins in treating patients with type 2 DM. Gliptins are dipeptidyl-peptidase 4 (DPP4/CD26) inhibitors, which stabilize glucagon-like peptide-1 (GLP-1), thereby increasing the bioavailability of insulin. Moreover, blocking DPP4 results in increased levels of stromal cell derived factor 1 (SDF-1). SDF-1 has been shown in pre-clinical animal studies to improve heart function and survival after myocardial infarction, and to promote arteriogenesis, the growth of natural bypasses, compensating for the function of an occluded artery. Clinical trials, however, failed to demonstrate a superiority of gliptins compared to placebo treated type 2 DM patients in terms of cardiovascular (CV) outcomes. This review highlights the function of DPP4 inhibitors in type 2 DM, and in treating cardiovascular diseases, with special emphasis on arteriogenesis. It critically addresses the potency of currently available gliptins and gives rise to hope by pointing out the most relevant questions that need to be resolved.

Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions

“…Atherosclerosis, the main underlying factor of CVD, is considered to be a chronic inflammatory disease with various cell types involved in this pathogenic process including differentially activated T and B lymphocytes, monocytes and macrophages, DCs, neutrophils, and endothelial cells (Rafieian-Kopaei, Setorki, Doudi, Baradaran, & Nasri, 2014). Abundant pre-clinical evidences implicate the beneficial role of DPP4 inhibition in atherosclerosis and CVD, which has been summarized by several reviews (Aroor, Manrique-Acevedo, & DeMarco, 2018;Avogaro & Fadini, 2014Vedantham, Kluever, & Deindl, 2018;Zhong, Maiseyeu, Davis, & Rajagopalan, 2015).…”

Successful revascularization versus medical therapy in diabetic patients with stable right coronary artery chronic total occlusion: a retrospective cohort study

“…Diabetes mellitus is observed in 34–40% CTO patients [12, 13]. The coexistence of diabetes is often associated with a severe coronary situation, which is characterized by endothelial cell dysfunction, microcirculation disorders, high-grade coronary atherosclerosis, a rapid progression of atherosclerosis and poor clinical outcomes [14–18]. Previous studies demonstrated clinical benefits after successful CTO revascularization [12, 19, 20].…”

Glycemic Control Status and Long-term Clinical Outcomes in Diabetic Chronic total occlusion patients: An Observational Study

“…In CTO lesions, the normal coronary blood ow is completely occluded, and the majority of patients develop compensating vascular collateralization to supply ischemic distal tissue (7,10). Vascular collateralization is a response to slow progressive stenosis; given the prolonged duration of stenosis formation, blood ow is redirected into pre-existing collateral arteries bypassing the occluded artery (9).…”

“…However, microcirculation is also involved in the progression of CTO. Collateral circulation, a form of microcirculation (8), also plays an important role in irrigating viable myocardium of the CTO territory and indeed in uences clinical prognosis (7,9,10). Unfortunately, collateral circulation is impaired in diabetic patients (11,12).…”