Role of Genetic Polymorphism of Angiotensin-Converting Enzyme, Plasminogen Activator Inhibitor-1 and Endothelial Nitric Oxide Synthase in the Prognosis of Coronary Artery Disease

Zhang, Ai Yuan; Ji, Xiang; Zhang, Ai Juan; Guan, Li; Jing, Huang; Wang, Jing-Xian

doi:10.4021/cr108e

Cited by 6 publications

(5 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Many genes related to extracellular matrix, coagulation or healing after vascular injury were also differentially regulated (Fgb, Kng1, Serpine-1). Serpine-1 encodes protein plasminogen activator inhibitor-1, which inhibits cell migration 36 and its loss-of-function variant is associated with high cardiovascular risk 37 . Additionally, several smooth muscle cell and vascular function related genes were downregulated.…”

Section: Discussionmentioning

confidence: 99%

Alternate models of acute dyslipidemia reveal divergent pathways upon atherosclerosis initiation

Hellberg

Shavva

Metso

et al. 2020

Preprint

View full text Add to dashboard Cite

Atherosclerosis is thought to be initiated by the sub-intimal retention of apolipoprotein-B containing lipoproteins within susceptible sites of the vasculature. Understanding this initiation is not possible with current legacy mouse models of atherosclerosis. We created two mouse strains of inducible hypercholesterolemia based on conditional loss of apolipoprotein E or through inducible expression of a gain-of-function proprotein convertase subtilisin/kexin type 9 D374Y mutation. Both strains rapidly broke plasma-lipid homeostasis and converted to a state of atherogenic dyslipidemia, resulting in overt aortic-accumulation of lipoproteins within 10 days. RNA-sequencing revealed that the vascular response is completely dependent on the route taken to dyslipidemia, which nevertheless implicates known pathogenic pathways in the aetiology of atherosclerosis, and further implicates APOE as an inhibitor of inflammation. As atherosclerosis develops, a convergence of common mechanistic processes emerge in both strains with significant involvement of the immune system, and targeting of CD8 T cells can regulate a conserved aortic response. Our results define atherosclerosis initiation as highly heterogeneous process and identify multiple potential therapeutic targets that may influence disease onset.

show abstract

Section: Discussionmentioning

confidence: 99%

Alternate models of acute dyslipidemia reveal divergent pathways upon atherosclerosis initiation

Hellberg

Shavva

Metso

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…This resulted in the hypertrophy of the muscle and caused the instability of the atherosclerosis plaque, and was subsequently followed by unstable angina or MI. In the same study [ 69 ], the prevalence of 4G/4G genotype was significantly higher in the MACE patients, and 4G/4G genotype was more frequent in multiple vessel disease than in single vessel disease.…”

Section: Discussionmentioning

confidence: 86%

“…Survival rate of carriers with ACE Del/Del genotype was reported to be significantly lower than that of Ins/Del and Ins/Ins carriers [ 68 ]. Zhang et al [ 69 ] clearly showed, in a group of 155 patients with CAD, that major adverse cardiovascular events (MACE) occurred more frequent in patients with the Del/Del genotype of the ACE gene. In fact, the increased activity of ACE by the Del allele led to the increased production of angiotensin II and enhanced the degradation of the cardiovascular protective agent bradykinin.…”

Section: Discussionmentioning

confidence: 99%

High Incidence of ACE/PAI-1 in Association to a Spectrum of Other Polymorphic Cardiovascular Genes Involving PBMCs Proinflammatory Cytokines in Hypertensive Hypercholesterolemic Patients: Reversibility with a Combination of ACE Inhibitor and Statin

et al. 2015

View full text Add to dashboard Cite

Cardiovascular diseases (CVDs) are significantly high in the Lebanese population with the two most predominant forms being atherosclerosis and venous thrombosis. The purpose of our study was to assess the association of a spectrum of CVD related genes and combined state of hypertension hypercholesterolemia (HH) in unrelated Lebanese. Twelve polymorphisms were studied by multiplex PCR and reverse hybridization of DNA from 171 healthy individuals and 144 HH subjects. Two genes were significantly associated with HH: ACE (OR: 9.20, P<0.0001) and PAI-1 (OR: 2.29, P = 0.007), respectively with the occurrence of the risky alleles “Del” and “4G”. The frequencies of the Del and 4G alleles were found to be 0.98 and 0.90 in the HH group versus 0.84 and 0.79 in the healthy group, respectively. Serum ACE activity and PAI-I increased significantly with Del/Del and 4G/5G genotypes. The co-expression of Del/4G(+/+) was detected in 113 out of 171 (66.0%) controls and 125 out of 144 (86.8%) HH subjects. Del/4G(-/-) was detected in only 6 (3.5%) controls and undetected in the HH group. Three venous thrombosis related genes [FV(Leiden), MTHFR(A1298C) and FXIII(V34L)] were significantly related to the prominence of the co-expression of Del/4G(+/+). A range of 2 to 8 combined polymorphisms co-expressed per subject where 5 mutations were the most detected. In Del/4G(+/+) subjects, peripheral blood mononuclear cells (PBMCs) produced significant elevated levels of IFN-γ and TNF-α contrary to IL-10, and no variations occurred for IL-4. ACE inhibitor (ramipril) in combination with statin (atorvastatin) and not alone reversed significantly the situation. This first report from Lebanon sheds light on an additional genetic predisposition of a complex spectrum of genes involved in CVD and suggests that the most requested gene FVL by physicians may not be sufficient to diagnose eventual future problems that can occur in the cardiovascular system. Subjects expressing the double mutations (Del/4G) are at high risk for the onset of CVDs.

show abstract

“…Several studies linked the increased ACE concentrations with the DD genotype, CAD [ 55 ], hypertension [ 56 ], autoimmune diseases [ 57 , 58 ] and acute respiratory distress syndrome [ 59 ]. Moreover, Zhang et al [ 60 ] reported that the DD genotype was more frequent in patients with major adverse CV events among CAD patients. On the other hand, there are studies that did not find any association of ACE I/D polymorphism and serum ACE levels in septic patients [ 61 ], age-related muscular degeneration [ 62 ] and patients with venous thromboembolism [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Biomarkers and Gene Polymorphisms in Members of Long- and Short-lived Families: A Longevity Study

Kolovou

Diakoumakou

Papazafiropoulou

et al. 2018

TOCMJ

View full text Add to dashboard Cite

Background:The influence of biomarkers in human lifespan has been investigated but with no clear results yet.Materials and methods:Lipids, Uric Acid (UA), Adiponectin (ADIPOQ), Insulin-like Growth Factor (IGF-1), cholesteryl ester transfer protein (CETP) and angiotensin-converting enzyme (ACE) proteins, as well as CETP, ADIPOQ, insulin-like growth factor binding protein-3 (IGFBP3) and ACE-gene polymorphisms were evaluated in 149 Greek individuals. The Long-Lived Families (LON) (n=84) comprised of 3 generations: long-lived aged ≥90 years (P), offspring (FL1) and their grandchildren (FL2), while the Short-Lived Families (EAD) (n=65) where both parents died <75 years, comprised of 2 generations: middle-aged (FD1) and children (FD2).Results:Serum CETP and IGF-1 levels were lower, whereas AdipoQ concentrations were higher in P compared with FL1 and FL2 members (CETP: p = 0.03 for both comparisons; IGF-1 p < 0.001 for both comparisons and ADIPOQ: p = 0.001 and p = 0.004, respectively). Furthermore, serum triglycerides, UA and glucose concentrations were higher in FD1 compared with FD2 subjects (p=0.001, 0.02 and ≤0.001, respectively). In FD2 and FL2, CETP levels were lower in individuals with B2B2 compared with B1B1 genotype (p=0.007). Additionally, ACE concentrations were higher in individuals with DD compared with II genotype in both Families (p=0.001). After adjustment for age and gender, CETP levels were lower in P and FL2 individuals with B2B2 compared with the B1B1 genotype (p=0.004 and 0.007, respectively).Conclusion:Increase serum TGs, UA and GL concentrations were higher in the middle-aged individuals compared with their children in families independently of their lifespan. The serum adiponectin concentration was the highest in the oldest old individuals implying beneficial influence on lifespan. Independently of family’s lifespan history, the youngest individuals with CETPB2B2 genotype, compared with individuals with CETPB1B1 genotypes, had lower serum CETP concentrations. The knowledge of the unfavourable gene(s)influencing human lifespan may be helpful in encouraging individuals to follow healthier lifestyle habits and better control their high-risk biomarkers.

show abstract

Role of Genetic Polymorphism of Angiotensin-Converting Enzyme, Plasminogen Activator Inhibitor-1 and Endothelial Nitric Oxide Synthase in the Prognosis of Coronary Artery Disease

Cited by 6 publications

References 28 publications

Alternate models of acute dyslipidemia reveal divergent pathways upon atherosclerosis initiation

Alternate models of acute dyslipidemia reveal divergent pathways upon atherosclerosis initiation

High Incidence of ACE/PAI-1 in Association to a Spectrum of Other Polymorphic Cardiovascular Genes Involving PBMCs Proinflammatory Cytokines in Hypertensive Hypercholesterolemic Patients: Reversibility with a Combination of ACE Inhibitor and Statin

Biomarkers and Gene Polymorphisms in Members of Long- and Short-lived Families: A Longevity Study

Contact Info

Product

Resources

About