Dipeptidyl Peptidase 4 Inhibition Alleviates Shortage of Circulating Glucagon-Like Peptide-1 in Heart Failure and Mitigates Myocardial Remodeling and Apoptosis via the Exchange Protein Directly Activated by Cyclic AMP 1/Ras-Related Protein 1 Axis

Abstract

This study was conducted to address the essential effect of the DPP4i on myocardium in terms of cardiac function and remodeling using nondiabetic mice with pressure overload (thoracic aortic constriction [TAC]). We unexpectedly found the pathological decline in casual GLP-1 level with concomitant reduction of its second messenger cyclic AMP (cAMP) concentration in myocardium of TAC, which was prevented by ALO. In the context of exploring the molecular mechanism(s) underlying the GLP-1/cAMP pathway, we found that the GLP-1-induced cAMP elevation diversely signals not only protein kinase A (PKA) but also exchange protein directly activated by cAMP 1 (EPAC1). Furthermore, we found that

The contributions of dipeptidyl peptidase IV to inflammation in heart failure

“…Emerging evidence suggests that DPPIV inhibitors, also known as gliptins, may provide cardiovascular benefits beyond glycemic control (1,3,4,13,23,40). In fact, genetic deletion or pharmacological inhibition of DPPIV improves cardiovascular outcomes after myocardial infarction in both normoglycemic and diabetic mice (42).…”

Multimodality Molecular Imaging of Cardiovascular Disease Based on Nanoprobes

“…Thus, the macrophage content in atherosclerotic plaques is an important contributor to atherosclerotic plaque instability. For above reasons, it is extremely urgent and necessary to develop effective molecular imaging 64 Cu-TNP by the aortic root and arch in atherosclerotic arteries model of apoE -/-mice, which was further demonstrated on in vivo MRI imaging (Fig. 1).…”

“…Ciesienski et al described the synthesis of three new fibrin-targeted PET probes: FBP1, FBP2 and FBP3, and then using them to image arterial thrombus in the rat models by using in vivo PET/MRI. Three fibrin-specific target peptides were labeled with 64 Cu after the conjugation with 1, 4,7, 10-tetraaza-cyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA). For MR angiography imaging, the results showed that there was an occlusion in the right carotid artery at the site of crush injury, and this vessel occlusion corresponds to the high radioactivity uptake displayed on PET images [32] (Fig.…”

“…4). And Ni et al generated a 64 Cu labeled folate-conjugated porphyrin nanoparticle suitable for multimodal non-invasive active macrophage tracking post-myocardial infarction (MI) [46]. In conclusion, multimodal molecular imaging tools based on nanotechnology may enable researchers to noninvasively image myocardial macrophage infiltration in the infracted myocardium in both the research and clinical settings.…”

“…It is literatured that atrial natriuretic peptide and C-type natriuretic peptide can suppress signaling of vascular endothelial growth factor (VEGF) to inhibit angiogenesis [55], which have been broadly investigated for their potential therapeutic effect [56]. To this end, Michael and his co-workers recently reported that small-molecule 64 Cu-labeled C-type atrial natriuretic factor (CANF) was an applicable and promising probe for PET imaging of NPR-C in atherosclerosis model [57]. Moreover, they developed and synthesized a multifunctional CANF-conjugated comblike nanoprobe, which was used to image NPR-C receptors during angiogenesis in a mouse model of hind limb ischemia with the use of micro PET/CT scan [58].…”