The Role of Vildagliptin in Treating Hypertension Through Modulating Serum VEGF in Diabetic Hypertensive Patients

El-Naggar, Abdel Rahman; Zaafar, Dalia; El-Yamany, Mohammed F.; Hassanin, Soha Osama; Bassyouni, Atef; Abdellatif, H.

doi:10.1177/1074248418817345

Cited by 5 publications

(3 citation statements)

References 18 publications

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“…Last but not least, vildagliptin demonstrated an antihypertensive effect through modulating serum vascular endothelial growth factor (VEGF) in diabetic hypertensive patients. Elevating VEGF levels improve physiological angiogenesis and vasculature [34]. VEGF signaling pathway inhibitors (VSP) have been approved for treatment of a number of different malignancies.…”

Section: Vascular Dilatation and Blood Pressurementioning

confidence: 99%

Vasculoprotective Effects of Vildagliptin. Focus on Atherogenesis

Wiciński

Górski

Wódkiewicz

et al. 2020

IJMS

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Vildagliptin is a representative of Dipeptidyl Peptidase-4 (DPP-4) inhibitors, antihyperglycemic drugs, approved for use as monotherapy and combination therapy in type 2 diabetes mellitus. By inhibiting enzymatic decomposition, DPP-4 inhibitors increase the half-life of incretins such as GLP-1 (Glucagon-like peptide-1) and GIP (Gastric inhibitors polypeptide) and prolong their action. Some studies present results suggesting the anti-sclerotic and vasculoprotective effects of vildagliptin reaching beyond glycemic control. Vildagliptin is able to limit inflammation by suppression of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathway and proinflammatory agents such as TNF-α (tumor necrosis factor α), IL-1β (Interleukin-1β), and IL-8 (Interleukin 8). Moreover, vildagliptin regulates lipid metabolism; attenuates postprandial hypertriglyceridemia; and lowers serum triglycerides, apolipoprotein B, and blood total cholesterol levels. This DPP-4 inhibitor also reduces macrophage foam cell formation, which plays a key role in atheromatous plaque formation and stability. Vildagliptin reduces vascular stiffness via elevation of nitric oxide synthesis, improves vascular relaxation, and results in reduction in both systolic and diastolic blood pressure. Treatment with vildagliptin lowers the level of PAI-1 presenting possible antithrombotic effect. By affecting the endothelium, inflammation, and lipid metabolism, vildagliptin may affect the development of atherosclerosis at its various stages. The article presents a summary of the studies assessing vasculoprotective effects of vildagliptin with special emphasis on atherogenesis.

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Section: Vascular Dilatation and Blood Pressurementioning

confidence: 99%

Vasculoprotective Effects of Vildagliptin. Focus on Atherogenesis

Wiciński

Górski

Wódkiewicz

et al. 2020

IJMS

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“…Inhibition of DPP4 also exerts a crucial role in endothelial growth and may serve as a recovery tool for diabetic vascular complications (37). In addition to treating type 2 diabetes, DPP4 is reported to improve the function of endothelial cells (38). These findings indicate that MCM3AP-AS1 and DPP4 might be involved in the prognosis of ccRCC by interacting with E2F1.…”

Section: Discussionmentioning

confidence: 99%

Pro-Angiogenic and Pro-Inflammatory Regulation by lncRNA MCM3AP-AS1-Mediated Upregulation of DPP4 in Clear Cell Renal Cell Carcinoma

Qiu

Yang

et al. 2020

Front. Oncol.

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Clear cell renal cell carcinoma (ccRCC) represents the most common type of renal cell carcinoma (RCC) in adults, in addition to the worst prognosis among the common epithelial kidney tumors. Inflammation and angiogenesis seem to potentiate tumor growth and metastasis of the malignancy. The current study explored the contributions of the lncRNA MCM3AP-AS1 in tumor-associated inflammation and angiogenesis in ccRCC with a specific focus on its transcriptional regulation and its interactions with transcription factor E2F1 and DPP4. Tumor tissues and matched adjacent non-tumor tissues were collected from 78 ccRCC patients. Methylation-specific PCR and ChIP assays were applied to detect the methylation at the promoter region of MCM3AP-AS1. Dual-luciferase reporter assay, RIP, RNA pull-down, and ChIP assays were employed to confirm the interactions between MCM3AP-AS1, E2F1, and DPP4. Nude mice were subcutaneously xenografted with human ccRCC cells. Cell proliferation was evaluated by CCK-8 assays and EDU staining in ccRCC cells in vitro and by immunohistochemical staining of Ki67 in vivo. Inflammation was examined by detecting the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). Pro-angiogenic ability of ccRCC cells was assessed by the co-culture with human umbilical vein endothelial cells (HUVEC) in vitro and by microvessel density (MVD) measurements and angiogenesis in the chicken chorioallantoic membrane. MCM3AP-AS1 was highly-expressed in ccRCC and associated with poor patient survival. Demethylation of MCM3AP-AS1 was noted in ccRCC tissues and cells. Over-expression of MCM3AP-AS1 enhanced cell proliferation, the release of pro-inflammatory cytokines, and the tube formation of HUVECs in cultured human Caki-1 and 786-O cells. MCM3AP-AS1 was shown to enhance the E2F1 enrichment at the DPP4 promoter, to further increase the expression of DPP4. Knockdown of DPP4 could abate pro-angiogenic and pro-inflammatory abilities of MCM3AP-AS1 in ccRCC cells. Pro-angiogenic and pro-inflammatory abilities of MCM3AP-AS1 in vivo were confirmed in mice subcutaneously xenografted with human ccRCC cells. Our findings demonstrate a novel mechanism by which lncRNA MCM3AP-AS1 exerts pro-angiogenic and pro-inflammatory effects, highlighting the potential of MCM3AP-AS1 as a promising target for treating ccRCC.

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“…Additionally, in diabetic rats, sitagliptin prevented the expression of endothelin-1 (ET-1) in the aortic endothelium via inhibiting the NF-κB/inhibitor of the NF-κB system by activation of the AMPK pathway, which produces a vascular protection function against hypertension ( 114 ). Lastly, vildagliptin performed an antihypertensive action via regulating circulating VEGF levels in patients with diabetes and hypertension ( 115 ).…”

Section: The Role Of Dpp4 Inhibitors In Vascular Aging-related Diseasesmentioning

confidence: 99%

Roles and Mechanisms of Dipeptidyl Peptidase 4 Inhibitors in Vascular Aging

Cao

Zhu

et al. 2021

Front. Endocrinol.

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Vascular aging is characterized by alterations in the constitutive properties and biological functions of the blood vessel wall. Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are indispensability elements in the inner layer and the medial layer of the blood vessel wall, respectively. Dipeptidyl peptidase-4 (DPP4) inhibitors, as a hypoglycemic agent, play a protective role in reversing vascular aging regardless of their effects in meliorating glycemic control in humans and animal models of type 2 diabetes mellitus (T2DM) through complex cellular mechanisms, including improving EC dysfunction, promoting EC proliferation and migration, alleviating EC senescence, obstructing EC apoptosis, suppressing the proliferation and migration of VSMCs, increasing circulating endothelial progenitor cell (EPC) levels, and preventing the infiltration of mononuclear macrophages. All of these showed that DPP4 inhibitors may exert a positive effect against vascular aging, thereby preventing vascular aging-related diseases. In the current review, we will summarize the cellular mechanism of DPP4 inhibitors regulating vascular aging; moreover, we also intend to compile the roles and the promising therapeutic application of DPP4 inhibitors in vascular aging-related diseases.

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The Role of Vildagliptin in Treating Hypertension Through Modulating Serum VEGF in Diabetic Hypertensive Patients

Cited by 5 publications

References 18 publications

Vasculoprotective Effects of Vildagliptin. Focus on Atherogenesis

Vasculoprotective Effects of Vildagliptin. Focus on Atherogenesis

Pro-Angiogenic and Pro-Inflammatory Regulation by lncRNA MCM3AP-AS1-Mediated Upregulation of DPP4 in Clear Cell Renal Cell Carcinoma

Roles and Mechanisms of Dipeptidyl Peptidase 4 Inhibitors in Vascular Aging

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