Biochemical and genetic role of apelin in essential hypertension and acute coronary syndrome

Gupta, Mohit; Mp, Girish; Shah, Drishti; Rain, Manjari; Mehta, Vimal; Tyagi, Sanjay; Trehan, Vijay; Pasha, Qadar

doi:10.1016/j.ijcard.2016.07.242

Cited by 27 publications

(20 citation statements)

References 21 publications

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“…Table 1A , 1B and 1C jointly show the baseline characteristics of 9 articles that assessed circulating apelin concentration between CAD patients and controls [ 13 , 15 , 16 , 18 – 23 ]. As 2 articles provided the results by CAD subtypes [ 16 , 18 ] and 1 article by sex [ 23 ], there were 13 studies in pooled analysis, including 1021 CAD patients and 654 controls. Year of publication ranged from 2010 to 2016.…”

Section: Resultsmentioning

confidence: 99%

Association of apelin and apelin receptor with the risk of coronary artery disease: a meta-analysis of observational studies

Chen

Lin

2017

Oncotarget

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It is well established that apelin-APLNR (apelin receptor) pathway plays a central role in cardiovascular system. In this meta-analysis, we summarized published results on circulating apelin concentration in association with coronary artery disease (CAD), apelin and APLNR genetic polymorphism(s) in predisposition to CAD risk and circulating apelin changes after surgical treatment for CAD. The results from 15 articles were pooled. Two authors independently took charge of literature search, article selection and information collection. Overall, circulating apelin concentration was significantly lower in CAD patients (N=1021) than in controls (N=654) (weighted mean difference [WMD]: -1.285 ng/mL, 95% confidence interval [CI]: -1.790 to -0.780, P<0001), with significant heterogeneity (I2=99.3%) but without publication bias. For the association of APLNR gene rs9943582 polymorphism with CAD (patients/controls: 5975/4717), the mutant T allele was associated with a 5.2% increased risk relative to the wild C allele (odds ratio: 1.052, 95% CI: 0.990 to 1.117, P=0.100), without heterogeneity (I2=0.0%) or publication bias. Circulating apelin was increased significantly after surgical treatment for CAD (N=202) (WMD: 2.011 ng/mL, 95% CI: 0.541 to 3.481, P=0.007), with significant heterogeneity (I2=98.0%). Stratified analyses showed that circulating apelin was significantly reduced in studies with age- and sex-matched patients and controls (WMD: -1.881 ng/mL, 95% CI: -2.457 to -1.304, P<0.001) and with total sample size ≥125 (WMD: -1.657 ng/mL, 95% CI: -2.378 to -0.936, P<0.001), relative to studies without matching reports and with total sample size <125. In brief, our results suggested that circulating apelin was a prominent athero-protective marker against the development of CAD.

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Section: Resultsmentioning

confidence: 99%

Association of apelin and apelin receptor with the risk of coronary artery disease: a meta-analysis of observational studies

Chen

Lin

2017

Oncotarget

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“…The Apelin-APJ polymorphisms also were reported with low Apelin 13 levels and the risk of hypertension. 77 The risk alleles include Apelin rs3115757C, rs56204867C and rs3761581A. 78 DOI: 10.1177/2045894020913475…”

Section: Allele-dependent Control Of Apelin and Nitric Oxide Signalingmentioning

confidence: 99%

Vascular homeostasis at high‐altitude: role of genetic variants and transcription factors

et al. 2020

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total number of manuscript pages -41 • total number of figures -4 • word count for the body of the text -7834 • type of contribution -review article AbstractHigh-altitude pulmonary edema (HAPE) occurs most frequently in non-acclimatized low landers on exposure to altitude ≥2500m. HAPE is a complex condition that involves perturbation of signaling pathways in vasoconstrictors, vasodilators, anti-diuretics and vascular growth factors. Genetic variations are instrumental in regulating these pathways and evidence is accumulating for a role of epigenetic modification in hypoxic responses. This review focuses on the crosstalk between HAPE-associated genetic variants and transcription factors, comparing high-altitude adapted and HAPE-afflicted subjects. This approach might ultimately yield biomarker information both to understand and to design therapies for high altitude adaptation.Evolution and physiological adaptation have permitted survival at the highest topographically elevated regions of the world. [1][2][3][4][5] Reduced air pressure at high-altitude decreases the partial pressure of inspired oxygen, affecting lungs, brain, heart and blood and can lead to a spectrum of high-altitude disorders including high-altitude pulmonary edema (HAPE), acute mountain sickness (AMS) and high-altitude cerebral edema (HACE). 6,7 This review focuses on HAPE. HAPE is a consequence of hypoxic pulmonary vasoconstriction leading to increased pulmonary arterial pressure and capillary stress failure. 8-11 HAPE victims have lower arterial oxygen saturation (SaO2) and higher heart rate, pulmonary vascular resistance and pulmonary vascular resistance index 12,13 than do unaffected sojourners to altitude. Clinically HAPE is characterized by dyspnoea, elevated body temperature, pink frothy sputum, tachypnoea, tachycardia, persistent cough and cyanosis. [14][15][16][17] Chest X-rays and CT scans show increased lung vascular markings and patchy shadows. 18,19 There have been great strides in understanding the clinical and physiological mechanisms of HAPE that has led to the discovery of successful treatments. Information on genetic contributions to this disorder has also grown rapidly over the last decade, partly to the development and implementation of newer genetic techniques. Candidate-gene approaches, advanced techniques such as Next-GenerationSequencing and Genome-Wide Association Studies have led to association of multiple genetic variants with high-altitude adaptation or maladaptation. [20][21][22][23][24][25][26] The majority of these genes belong to multiple, frequently related pathways. These include the renin-angiotensin aldosterone system, apelin signaling, nitric oxide signaling, and hypoxia induced signaling.These pathways regulate vasoactive molecules including angiotensin II, apelin, nitric oxide, aldosterone, and beta-adrenergics. [27][28][29][30][31] In addition to genetic variation, epigenetics plays prominent role in HAPE and other diseases. [32][33][34][35] DNA methylation, acetylation, histone modifications/chromatin rem...

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“…The apelinergic systemic is important for the activation of eNOS production, and hence vasodilation (Kim 2014), and the integrity of the endothelial barrier through modulating KLF-2 (Lin et al 2010). Hence, deficiencies in apelin have been linked to increasing severity of cardiopulmonary diseases (Fan et al 2015;Gupta et al 2016). Additionally, it has been recently reported that high-altitude pulmonary edema is positively associated with apelin gene variants as well as increased CpG methylation in humans (Mishra et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Acute inhalation of ozone induces DNA methylation of apelin in lungs of Long-Evans rats

Miller

Dye

Schladweiler

et al. 2018

Inhalation Toxicology

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Apelin has cardiopulmonary protective properties that promote vasodilation and maintenance of the endothelial barrier. While reductions in apelin have been identified as a contributor to various lung diseases, including pulmonary edema, its role in the effect of air pollutants has not been examined. Thus, in the current study, we sought to investigate if apelin is a downstream target of inhaled ozone and if such change in expression is related to altered DNA methylation in the lung. Male, Long-Evans rats were exposed to filtered air or 1.0 ppm ozone for 4 h. Ventilation changes were assessed using whole-body plethysmography immediately following exposure, and markers of pulmonary edema and inflammation were assessed in the bronchoaveolar lavage (BAL) fluid. The enzymatic regulators of DNA methylation were measured in the lung, along with methylation and hydroxymethylation of the apelin promoter. Data showed that ozone exposure was associated with increased enhanced pause and protein leakage in the BAL fluid. Ozone exposure reduced DNA cytosine-5-methyltransferase (DNMT) activity and Dnmt3a/b gene expression. Exposure-induced upregulation of proliferating cell nuclear antigen, indicative of DNA damage, repair, and maintenance methylation. Increased methylation and reduced hydroxymethylation were measured on the apelin promoter. These epigenetic modifications accompanied ozone-induced reduction of apelin expression and development of pulmonary edema. In conclusion, epigenetic regulation, specifically increased methylation of the apelin promoter downstream of DNA damage, may lead to reductions in protective signaling of the apelinergic system, contributing to the pulmonary edema observed following the exposure to oxidant air pollution.

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Biochemical and genetic role of apelin in essential hypertension and acute coronary syndrome

Cited by 27 publications

References 21 publications

Association of apelin and apelin receptor with the risk of coronary artery disease: a meta-analysis of observational studies

Association of apelin and apelin receptor with the risk of coronary artery disease: a meta-analysis of observational studies

Vascular homeostasis at high‐altitude: role of genetic variants and transcription factors

Acute inhalation of ozone induces DNA methylation of apelin in lungs of Long-Evans rats

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