scholarly journals Estrogen inhibits vascular calcification in rats via hypoxia-induced factor-1α signaling

Vascular ◽  
2020 ◽  
Vol 28 (4) ◽  
pp. 465-474
Author(s):  
Xinhua Wu ◽  
Qiuyan Zhao ◽  
Zhangrong Chen ◽  
Yong-Jian Geng ◽  
Wanting Zhang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Coronary Artery ◽  
Bone Morphogenetic Protein ◽  
Vascular Calcification ◽  
Coronary Artery Calcification ◽  
Bone Morphogenetic Protein 2 ◽  
Ovariectomized Rats ◽  
Sprague Dawley ◽  
Morphogenetic Protein

Objective Calcification serves as a surrogate for atherosclerosis-associated vascular diseases, and coronary artery calcification is mediated by multiple pathogenic factors. Estrogen is a known factor that protects the arterial wall against atherosclerosis, but its role in the coronary artery calcification development remains largely unclear. This study tested the hypothesis that estrogen inhibits coronary artery calcification via the hypoxia-induced factor-1α pathway. Methods Eight-week-old healthy female Sprague–Dawley rats were castrated, and vitamin D3 was administered orally to establish. Hypoxia-induced factor-1 inhibitor was administered to test its effect on vascular calcification and expression of bone morphogenetic protein 2 and runt-related transcription factor-2. Vascular smooth muscle cell calcification was induced with CaCl2 in rat aortic smooth muscle cells in the presence or absence of E2(17β-estradiol) and bone morphogenetic protein 2 siRNA intervention. Results The estrogen levels in ovariectomized rats were significantly decreased, as determined by ELISA. Expression of hypoxia-induced factor-1α mRNA and protein was significantly increased in vascular cells with calcification as compared to those without calcification ( p < 0.01). E2 treatment decreased the calcium concentration in vascular cell calcification and cell calcium nodules in vitro ( p <  0.05). E2 also lowered the levels of hypoxia-induced factor-1α mRNA and protein ( p <  0.01). Oral administration of the hypoxia-induced factor-1α inhibitor dimethyloxetane in castrated rats alleviated vascular calcification and expression of osteogenesis-related transcription factors, bone morphogenetic protein 2 and RUNX2 ( p <  0.01). Finally, bone morphogenetic protein 2 siRNA treatment decreased the levels of p-Smad1/5/8 in A7r5 calcification cells ( p <  0.01). Conclusion Estrogen deficiency enhances vascular calcification. Treatment with estrogen reduces the expression of hypoxia-induced factor-1α as well as vascular calcification in rats. The estrogen effects occur in a fashion dependent on hypoxia-induced factor-1α regulation of bone morphogenetic protein-2 and downstream Smad1/5/8.

scholarly journals Correlation between Systemic Arterial Hypertension and Bone Morphogenetic Protein-2 in Central Obese Non-Diabetic Men with Evidence of Coronary Artery Calcification

2011 ◽  
Vol 3 (3) ◽  
pp. 185
Author(s):  
Antonia Anna Lukito ◽  
Allen Widyasanto ◽  
Trilis Yulianti ◽  
Rusli Muljadi ◽  
Andi Wijaya ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Coronary Artery ◽  
Plasma Concentration ◽  
Bone Morphogenetic Protein ◽  
Coronary Artery Calcification ◽  
Subclinical Atherosclerosis ◽  
Coronary Calcification ◽  
Bone Morphogenetic Protein 2 ◽  
Systemic Hypertension ◽  
Morphogenetic Protein

BACKGROUND: Previous studies have confirmed separately the relationship between obesity, insulin-resistance, hypertension and bone morphogenetic protein-2 (BMP-2) with coronary artery calcification, a parameter of subclinical atherosclerosis. It was also reported that BMPs may function as proinflammatory, prohypertensive and proatherogenic mediators. The study aimed to assess the correlation between systemic hypertension and BMP-2 plasma concentration in central-obese non-diabetic men with evidence of coronary artery calcification.METHODS: This was a cross sectional study on 60 central-obese non-diabetic men, of an average age of 55.2 years, with evidence of coronary calcification, who came for health check-up and met the inclusion criteria consecutively as defined by waist circumference >90 cm and fasting blood glucose <126 mg/dL. Coronary calcification was defined by coronary artery calcium (CAC) score ≥10 Agatson-unit Dual Source 64 slice CT scan.RESULTS: There is positive correlation between hypertension and BMP-2 in central-obese non-diabetic men with evidence of coronary artery calcification. BMP-2 plasma concentration was higher in the hypertensive subjects. The correlation was stronger in younger (<55 years old) subjects and subjects with insulin-resitance.KEYWORDS: hypertension, BMP-2, coronary calcification, central obesity, age, insulin resistance

scholarly journals The Mechanism of Coronary Artery Calcification in Centrally Obese Non-Diabetic Men: Study on The Interaction of Leptin, Free Leptin Index, Adiponectin, hs-C Reactive Protein, Bone Morphogenetic Protein-2 and Matrix Gla Protein

2020 ◽  
Vol 4 (2) ◽  
pp. 88
Author(s):  
Antonia Anna Lukito ◽  
Syakib Bakri ◽  
Peter Kabo ◽  
Andi Wijaya
Keyword(s):  
Coronary Artery ◽  
Bone Morphogenetic Protein ◽  
Coronary Artery Calcification ◽  
Central Obesity ◽  
Matrix Gla Protein ◽  
Bone Morphogenetic Protein 2 ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Morphogenetic Protein ◽  
Hs Crp

Background: The calcium in the artery was thought to be the result of the imbalance or dysregulation of the promoter and inhibitor cytokines influenced by various subclinical and clinical conditions. This study aimed to investigate the interaction between central obesity, as an early subclinical condition, also known as a chronic low grade inflammation condition and coronary artery calcium (CAC) in non-diabetic population including the underlying pathomechanisms of a CAC in the early stage of atherosclerosis.Materials and Methods: This was a cross-sectional pathway analysis study enrolling 60 central obesity non-diabetic men that underwent coronary calcium score scan, anthropometrics and biomarker assays.Results: There was a positive correlation between increasing free leptin index/adiponectin (FLI/A) ratio and CAC (r=0.297; p<0.05). There was a positive correlation between increasing FLI/A ratio and plasma high sensitive C-reactive protein (hs-CRP) (r=0.318; p<0.05). Plasma hs-CRP and bone morphogenetic protein-2 (BMP-2)-matrix gla protein (MGP) dysregulation were positively correlated (r=0.221; p<0.05) after adjusted to risk factors including insulin resistance, hypertension, age, and dyslipidemia.Conclusion: The study found that one of the pathways involved in CAC in the centrally obese non-diabetic male is might be due to an increase of free leptin and decrease of adiponectin. The free leptin and adiponection ratio also increased hs-CRP, which partially correlated to the dysregulation of BMP-2 and MGP.Keywords: coronary artery calcification, central obesity, adipokines, bone regulator protein, pathomechanism

scholarly journals Procyanidin B2 Reduces Vascular Calcification through Inactivation of ERK1/2-RUNX2 Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 916
Author(s):  
Yingquan Liang ◽  
Guilan Chen ◽  
Feng Zhang ◽  
Xiaoxiao Yang ◽  
Yuanli Chen ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Calcification ◽  
Aortic Root ◽  
Smooth Muscle Actin ◽  
Bone Morphogenetic Protein 2 ◽  
Plaque Burden ◽  
Runx2 Expression ◽  
Plaque Instability ◽  
Related Transcription Factor

Vascular calcification is strongly associated with atherosclerotic plaque burden and plaque instability. The activation of extracellular signal-regulated kinase 1/2 (ERK1/2) increases runt related transcription factor 2 (RUNX2) expression to promote vascular calcification. Procyanidin B2 (PB2), a potent antioxidant, can inhibit ERK1/2 activation in human aortic smooth muscle cells (HASMCs). However, the effects and involved mechanisms of PB2 on atherosclerotic calcification remain unknown. In current study, we fed apoE-deficient (apoE−/−) mice a high-fat diet (HFD) while treating the animals with PB2 for 18 weeks. At the end of the study, we collected blood and aorta samples to determine atherosclerosis and vascular calcification. We found PB2 treatment decreased lesions in en face aorta, thoracic, and abdominal aortas by 21.4, 24.6, and 33.5%, respectively, and reduced sinus lesions in the aortic root by 17.1%. PB2 also increased α-smooth muscle actin expression and collagen content in lesion areas. In the aortic root, PB2 reduced atherosclerotic calcification areas by 75.8%. In vitro, PB2 inhibited inorganic phosphate-induced osteogenesis in HASMCs and aortic rings. Mechanistically, the expression of bone morphogenetic protein 2 and RUNX2 were markedly downregulated by PB2 treatment. Additionally, PB2 inhibited ERK1/2 phosphorylation in the aortic root plaques of apoE−/− mice and calcified HASMCs. Reciprocally, the activation of ERK1/2 phosphorylation by C2-MEK1-mut or epidermal growth factor can partially restore the PB2-inhibited RUNX2 expression or HASMC calcification. In conclusion, our study demonstrates that PB2 inhibits vascular calcification through the inactivation of the ERK1/2-RUNX2 pathway. Our study also suggests that PB2 can be a potential option for vascular calcification treatment.

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