DPP4 Activity, Hyperinsulinemia, and Atherosclerosis

Love, Kaitlin; Liu, Zhenqi

doi:10.1210/clinem/dgab078

Cited by 32 publications

(17 citation statements)

References 130 publications

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“…F11R is required for the proliferation and migration of inflamed smooth muscle cells, thereby playing an important role in the subsequent growth of atherosclerotic plaques ( Azari et al, 2010 ). DPP4 is a transmembrane serine protease that cleaves off N-terminal dipeptides ( Chitadze et al, 2021 ; Love and Liu, 2021 ), which are highly involved in glucose and insulin metabolism as well as in immune regulation. VAV3 encodes the protein of a Rho family GTPase that regulates cell signalling pathways, including those of T- and B-cell receptors, by mediating the activities of Rho family members ( Shen et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Immune-Related Gene Signature in Stanford Type A Aortic Dissection

Wang

et al. 2022

Front. Genet.

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Background: Stanford type A aortic dissection (ATAAD) is a common life-threatening event in the aorta. Recently, immune disorder has been linked to the risk factors that cause ATAAD at the molecular level. However, the specific immune-related gene signature during the progression is unclear.Methods: The GSE52093 and GSE98770 datasets related to ATAAD from the Gene Expression Omnibus (GEO) database were acquired. The immune gene expression levels were analyzed by single sample gene set enrichment analysis (ssGSEA). The correlations between gene networks and immune scores were determined by weighted gene correlation network analysis (WGCNA). The different immune subgroups were finally divided by consensus clustering. The differentially expressed genes (DEGs) were identified and subsequent functional enrichment analyses were conducted. The hub genes were identified by protein–protein interaction (PPI) network and functional similarities analyses. The immune cell infiltration proportion was determined by the CIBERSORT algorithm.Results: According to the ssGSEA results, the 13 ATAAD samples from the GEO database were divided into high- and low-immune subgroups according to the ssGSEA, WGCNA, and consensus clustering analysis results. Sixty-eight immune-related DEGs (IRDEGs) between the two subgroups were enriched in inflammatory-immune response biological processes, including leukocyte cell–cell adhesion, mononuclear cell migration, and myeloid leukocyte migration. Among these IRDEGs, 8 genes (CXCR4, LYN, CCL19, CCL3L3, SELL, F11R, DPP4, and VAV3) were identified as hub genes that represented immune-related signatures in ATAAD after the PPI and functional similarities analyses. The proportions of infiltrating CD8 T cells and M1 macrophages were significantly higher in ATAAD patients in the immune-high group than the immune-low group.Conclusion: Eight immune-related genes were identified as hub genes representing potential biomarkers and therapeutic targets linked to the immune response in ATAAD patients.

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Section: Discussionmentioning

confidence: 99%

Identification of Immune-Related Gene Signature in Stanford Type A Aortic Dissection

Wang

et al. 2022

Front. Genet.

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“…When both expression and shedding increase, the DPP4 concentration rises [ 18 ]. Several studies have established that the DPP4 activity is altered in some conditions such as obesity, non-alcoholic fatty liver, T2DM, and CAD [ 47 , 48 ]; however, data about the DPP4 concentrations are scarce and contradictory [ 18 ]. Gorrell et al reported that the serum DPP4 concentrations decrease in some pathological conditions except in those where a liver injury or extensive lymphocyte proliferation is involved [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Association of the rs17574 DPP4 Polymorphism with Premature Coronary Artery Disease in Diabetic Patients: Results from the Cohort of the GEA Mexican Study

et al. 2022

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Previously, it has been reported that hypoalphalipoproteinemia (HA) is associated with rs17574 DDP4 polymorphism. Considering that in diabetic patients, HA is often present and is a risk factor for premature coronary artery disease (pCAD), the study aimed to evaluate the association of this polymorphism with pCAD in diabetic individuals. We genotyped the rs17574 polymorphism in 405 pCAD patients with T2DM, 736 without T2DM, and 852 normoglycemic individuals without pCAD and T2DM as controls. Serum DPP4 concentration was available in 818 controls, 669 pCAD without T2DM, and 339 pCAD with T2DM. The rs17574 polymorphism was associated with lower risk of pCAD (padditive = 0.007; pdominant = 0.003, pheterozygote = 0.003, pcodominant1 = 0.003). In pCAD with T2DM patients, DPP4 levels were lower when compared with controls (p < 0.001). In the whole sample, individuals with the rs17574 GG genotype have the lowest protein levels compared with AG and AA (p = 0.039) carriers. However, when the same analysis was repeated separately in all groups, a significant difference was observed in the pCAD with T2DM patients; carriers of the GG genotype had the lowest protein levels compared with AG and AA (p = 0.037) genotypes. Our results suggest that in diabetic patients, the rs17574G DPP4 allele could be considered as a protective genetic marker for pCAD. DPP4 concentrations were lower in the diabetic pCAD patients, and the rs17574GG carriers had the lowest protein levels.

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Section: Dpp4: Structure and Functionsmentioning

confidence: 99%

“…The extracellular part consists of a flexible rod, a glycosylation rich region (binding region with anti-CD26 antibody, adenosine deaminase (ADA) and caveolin-1), a cysteine rich region (binding region with collagen and fibronectin) and a catalytic region composed of the catalytic triad Ser 630 , Asp 708 and His 740 . 14,15 DPP4 contains nine potential glycosylation sites for glycosylation modification. Among them, co-translational core N-glycosylation was significantly associated with DPP4 folding and stability, whereas N-terminal sialylation appeared to regulate more pathophysiological processes.…”

Section: Dpp4: Structure and Functionsmentioning

confidence: 99%

DPP4 as a Potential Candidate in Cardiovascular Disease

Chen¹,

Kong²,

Zhang³

et al. 2022

JIR

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The rising prevalence of cardiovascular disease has become a global health concern. The occurrence of cardiovascular disease is the result of long-term interaction of many risk factors, one of which is diabetes. As a novel anti-diabetic drug, DPP4 inhibitor has been proven to be cardiovascular safe in five recently completed cardiovascular outcome trials. Accumulating studies suggest that DPP4 inhibitor has potential benefits in a variety of cardiovascular diseases, including hypertension, calcified aortic valve disease, coronary atherosclerosis, and heart failure. On the one hand, in addition to improving blood glucose control, DPP4 inhibitor is involved in controlling cardiovascular risk factors. On the other hand, DPP4 inhibitor directly regulates the occurrence and progression of cardiovascular diseases through a variety of mechanisms. In this review, we summarize the recent advances of DPP4 in cardiovascular disease, aiming to discuss DPP4 inhibitor as a potential option for cardiovascular therapy.

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DPP4 Activity, Hyperinsulinemia, and Atherosclerosis

Cited by 32 publications

References 130 publications

Identification of Immune-Related Gene Signature in Stanford Type A Aortic Dissection

Identification of Immune-Related Gene Signature in Stanford Type A Aortic Dissection

Association of the rs17574 DPP4 Polymorphism with Premature Coronary Artery Disease in Diabetic Patients: Results from the Cohort of the GEA Mexican Study

DPP4 as a Potential Candidate in Cardiovascular Disease

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