Roles and Mechanisms of Dipeptidyl Peptidase 4 Inhibitors in Vascular Aging

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  Figure 1. Roles and mechanisms of DPP4 inhibitors in vascular aging -related diseases. DPP4 inhibitors play an effective effect against vascular aging-related diseases through multiple mechanisms. AS, atherosclerosis; JMT, intima-media thickness; PWV, pulse wave velocity; LV, left ventricular; CM, chylomicrons; VLDL, very low density lipoprotein; IDL, intermediate density lipoprotein; TG, triglyceride; TC, total cholesterol; FFA, free fatty acid; apoB48, apolipoprotein B-48; HDL-C, high-density lipoprotein cholesterol; MMP2, macrophage matrix metalloprotcinase-2; MMP9, macrophage matrix metalloproteinasc-9; ER, endoplasmic reticulum; eNOS, endothelial nitric oxide synthase; ACEs, angiotensin-converting enzymes; ET-1, endothelin-1 ; VEGF, vascular endothelial growth factor; TRAF3IP2,TRAF3, Interacting Protein 2; SDF-1, stromal cell-derived factor-Iα; CXCR4, C-X-C chemokine receptor type-4; GLP-1 , glucagon-like peptide-1; GLP-2, glucagon-like peptide-2; Angptl3, angiopoietin-like 3; Bhmt, betaine-homocysteine S-mcthyltransferasc; Pon1, paraoxonasc-1; Nurrl, nuclear receptor related I ; PINK1, PTEN-i nduced putative kinase 1; Nrf2, nuclear factor erythroid 2-related factor 2; PI3K,…

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  Figure 2. The mechanisms of DPP4 inhibitors in vascular aging and vascular aging-related diseases. DPP4 inhibitors play a beneficial effect in vascular aging not only through multiple cellular mechanisms, including improving ECs function, increasing EPCs count, mediating the process of monocyte attachment and decreasing VSMCs proliferation, but also through complex molecular mechanisms, including AP-I and NF-KB signaling, SDF-1α/CXCR4 axis and Akt/AMPK signaling pathway. Thereby preventing vascular aging-related diseases, compassing AS, hypertension, heart failure, dyslipidemia, neurodegenerative diseases and cerebrovascular diseases, psychological diseases. Arrows indicate stimulatory relationships, indicates inhibitory signal. AP-1, activator protein 1; NF-κB, nuclear factor kappaB; SDF-1, stromal cell- derived factor-1α; CXCR4, C-X-C chemokine receptor type-4; Akt, v-akt murine thymoma viral oncogene homologue; MAPK, mitogen-activated protein kinase; ECs, endothelial cells; VSMCs, vascular smooth muscle cells; EPCs, endothelial progenitor cell; AS, atherosclerosis. Arrows indicate stimulatory relationship, non-arrows indicate inhibitory signal.