scholarly journals Monoamine oxidase inhibition improves vascular function in mammary arteries from nondiabetic and diabetic patients with coronary heart disease

2016 ◽  
Vol 94 (10) ◽  
pp. 1040-1047 ◽  
Author(s):  
Rodica Lighezan ◽  
Adrian Sturza ◽  
Oana M. Duicu ◽  
Raluca A. Ceausu ◽  
Adrian Vaduva ◽  
...  

Monoamine oxidases (MAOs) are mitochondrial enzymes with 2 isoforms that have emerged as important contributors to cardiovascular oxidative stress via the constant generation of hydrogen peroxide. The present study was purported to assess whether MAO-derived H2O2 contributes to the endothelial dysfunction in mammary arteries harvested from coronary heart disease patients with and without diabetes mellitus subjected to coronary artery bypass grafting. To this aim, the effects of MAO inhibition on vascular contractility to phenylephrine and endothelial-dependent relaxation (EDR) in response to acetylcholine were studied in vascular segments. Clorgyline (irreversible MAO-A inhibitor), selegiline (irreversible MAO-B inhibitor), and moclobemide (reversible MAO-A inhibitor) were applied in the organ bath (10 μmol/L). MAO expression was assessed by immunohistochemistry. We found a constant impairment of EDR that has been significantly attenuated in the presence of the MAO-A and MAO-B inhibitors in both groups of coronary heart disease patients. MAO-B was the dominant isoform in all human diseased vessels. In conclusion, in vitro inhibition of MAO significantly improved EDR in human mammary arteries, regardless of the presence of diabetes. These data suggest that MAO inhibitors might be useful in restoring endothelial response in clinical conditions associated with increased oxidative stress, such as coronary artery disease and diabetes.

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
H A Morsy ◽  
L A Habib ◽  
E H Abdeldayem ◽  
A I Sayed

Abstract Diabetes is known to be a major cardiovascular risk factor associated with significantly increased morbidity and mortality and particularly increased risk of major cardiac events especially myocardial infarction as a manifestation of highly incident coronary artery disease (CAD).This can lead to decreased life expectation and life quality. Major cause for myocardial infarction is plaque rupture. Prevalence of obstructive and non-obstructive plaques is increased in diabetic patients. Background and Objectives The prevalence of coronary heart disease in diabetic patients compared to non- diabetics and evaluating the composition of the plaque in diseased individuals in both groups by usage of multislice computed tomography (MSCT) angiography . Subjects and Methods A total of 80 consecutive MSCT angiography examinations were performed between August 2017 and June 2018. Of these, the patients were evaluated for the presence and type of atherosclerotic plaque and severity of luminal narrowing. Results Eighty (40 in the diabetic group and 40 in the non-diabetic group) patients underwent MSCT angiography with DM prevalence of 0.212 (95% Cl for AOR 0.056 -1.896). Among them, 20 patients (50 %) in the diabetic group and 14 patients (35 %) in the non-diabetic group had +ve coronary heart disease, 33.3 % had significant and moderately significant coronary narrowing on diabetic group and 31.3 % in non-diabetic group on MSCT angiography. Diabetic patients had more soft plaque compared with non-diabetic patients. Conclusion DM is not an independent factor for the disease occurrence in coronary artery disease but is a dependent factor in the association of other risk factors such as smoking ,hypertension and dyslipidemia.


2021 ◽  
Author(s):  
Lexun Wang ◽  
DongXing Zhang ◽  
Wenjing Zhan ◽  
Jianying Yin ◽  
Ke Wang ◽  
...  

Abstract Background: Coronary heart disease (CHD) caused by diabetes mellitus (DM) is the main cause of death in diabetic patients. The treatment of diabetes complicated with coronary heart disease (DM-CHD) is still a big challenge in the medical practice. Endothelial-mesenchymal transition (EndMT) has been considered as the key process in endothelial dysfunction in the atherosclerotic diseases, including DM-CHD. The traditional Chinese prescription Fufang Zhenzhu Tiaozhi (FTZ) formula is used to treat diabetes and dyslipidemia. Recently, several studies have shown the therapeutic effect of FTZ in cardiovascular diseases. However, the mechanism of the protection on coronary atherosclerosis is still needed for further investigation.Objective: To evaluate the efficacy of FTZ in preventing DM-CHD and explore the specific mechanism of FTZ based on EndMT. Methods: DM-CHD minipigs model constructed by using high-fat/high-sucrose/high-cholesterol diet (HSFCD) combined with streptozotocin (STZ) and coronary balloon injury, then randomly divided into control (Ctrl), DM-CHD model (Mod), DM-CHD treated with FTZ (FTZ) or positive drug (metformin and atorvastatin, M+A). Twenty-two weeks after administration, the cardiac functions of pigs were detected by ultrasound and electrocardiography (ECG). The stenosis and plaque of the left anterior descending (LAD) coronary artery were assessed through angiography, intravascular ultrasound (IVUS), and optical coherence tomography (OCT). Pigs were sacrificed after all examinations and the tissues were collected for further testing. The serum levels of blood glucose and lipid, myocardial injury markers, and inflammatory factors were detected. The biomarkers of EndMT were observed. The potential targets and signaling pathways were analyzed. The human umbilical vein endothelial cell (HUVEC) was cultured for testing the effect of FTZ under high glucose (HG).Results: In the Mod group, the serum levels of FBG, TC, TG, HDL-C, and LDL-C and the myocardial injury markers (LDH, cTnT, CK-MB) were increased significantly. The ST segment and the height of the T wave of ECG were significantly elevated in the Mod group. The results of coronary angiography, OCT, and IVUS showed that there was an obvious narrow in the coronary artery of the Mod group, and the pathological changes were mainly intimal fibrosis. Furthermore, the levels of TGF-β1 and α-SMA significantly increased while the levels of CD31 and VE- cadherin notably decreased in the Mod group, which showed EndMT characteristic. Besides, the inflammation and apoptosis pathways were markedly activated in the Mod group. After treatment with FTZ, the glucolipid metabolism and the myocardium injury were effectively improved in DM-CHD minipigs. FTZ treatment improved the function of the heart and alleviated coronary stenosis. The expression of α-SMA in the coronary artery was significantly decreased, and the expression of CD31 and VE-cadherin were increased in the coronary artery of the FTZ group minipigs. In addition, FTZ treatement inhibited the expressions of the inflammatory relative protein p-IκB/p-NF-κB/IL-1β and the apoptosis proteins Bax/cleave-Caspase-3 in the coronary artery tissue. Additionally, FTZ ameliorated the injury effect and high migration activity of HUVECs caused by HG. Conclusions: Coronary atherosclearosis plaque formation is related to EndMT and FTZ protect heart partly via inhibiting coronary endothelial EndMT and regulating inflammation in DM-CHD pigs.


Author(s):  
Jia-Qi Yao ◽  
Zhuo-Jun Deng ◽  
Ming-Xing Fang ◽  
Na Xiao ◽  
Qing-Sheng Huang ◽  
...  

IntroductionThe present study was conducted to explore the expression of serum inflammatory cytokines and oxidative stress markers in patients with coronary heart disease (CHD), with an attempt to analyze their relationship with the coronary artery calcium score (CACS) by coronary computed tomography angiography (CCTA).Material and methodsIt total 81 patients with coronary heart disease and 81 healthy adults were included as the observation group and the control group, respectively. The levels of serum interleukin (IL)-6 and IL-12 of the two groups were detected by ELISA, and serum superoxide dismutase (SOD) was detected by the hydroxylamine oxidation method. Micro-RNA-497-5p (miR-497-5p) was screened out as a possible new CHD biomarker and its serum level was measured by real-time fluorescence quantitative PCR. The CACS of patients in the observation group was calculated by the Agatston method to analyze the correlation between the abovementioned indexes and CACS.ResultsWith increase in the number of CHD lesions, the levels of IL-6, IL-12 and miR-497-5p rose gradually while the level of SOD decreased gradually. In the observation group, IL-6, IL-12 and miR-497-5p were positively correlated with CACS while SOD was negatively correlated with CACS.ConclusionsAbnormal expression levels of serum IL-6, IL-12, SOD and miR-497-5p may be able to reveal the severity of the disease, and the combination with CACS is of potential value in terms of evaluating the condition of patients harboring coronary heart disease.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
I Leonova ◽  
S Boldueva ◽  
V Feoktistova ◽  
D Evdokimov

Abstract Funding Acknowledgements Type of funding sources: None. The widespread use of coronary angiography (CAG) in patients with acute coronary syndrome led to the understanding that in some patients myocardial infarction (MI) occurs against angiographically unchanged or slightly modified coronary arteries (CA). In such cases, the so-called "type 2 IM" is diagnosed in some patients, however, to determine the true cause of MI, a modern method of investigation such as optical coherence tomography (OCT) is needed to visualize the intima of the CA and detect a minimal atherosclerotic process.  The purpose of the study was to establish the etiology of MI without obstructive coronary artery disease (MINOCA) using OCT. Materials and methods 160 conclusions of the OCT were analyzed. In 9 (6%) cases, the study was conducted in patients who underwent proven MI (mean age 43,1 ± 13,2, 8 males, 1 female) who had no hemodynamically significant CA stenosis according to CAG data. Results in 2 cases (22%) patients had ST-elevation MI, thrombotic occlusion of the CA (in one case, thrombaspiration was performed). In both patients, spontaneous dissection of the intima of the unmodified CA was detected in the OCT. The remaining 7 patients had non-ST-elevation MI, and in 2 cases, a diagnosis of type 2 MI was established: in both patients, the atherosclerotic plaque was visualized, narrowing the lumen of the CA less than 50%, in one case MI developed against a background of the hypertensive crisis, in another - against a background of spasm of CA. In the remaining 5 patients, OCT revealed subintimal atheromatous, with elements of local dissection of the intima. Thus, in 78% of patients atherosclerosis of CA of different severity (from the subintimal deposition of lipids to the development of atherosclerotic plaque, narrowing the clearance of the SC by less than 50%) was diagnosed. In the analysis of risk factors for coronary heart disease (CHD), 57% of patients with atheromatous CA had more than 2 risk factors for CHD: 3 (42%) smoked, 5 (71%) - obesity, 4 (57% ) - had arterial hypertension, 3 (42%) had dyslipidemia, 1 (14%) had type 2 diabetes. In the group of patients with spontaneous intima dissection of the CA, 1 patient (woman) did not have CHD risk factors, the 2-nd suffered from obesity and hypertension. For all patients a lifestyle correction was recommended; statins, antiplatelets were prescribed, patients with spontaneous dissection of CA had the recommendation of examination in the medical-genetic center. Conclusion Based on the results of the study, in most cases, the cause of IMBOC development was an atherosclerotic lesion of the coronary arteries, which is not always visualized with standard coronary angiography. Basically, the patients were young and middle-aged. Most patients had different risk factors for coronary heart disease.


Sign in / Sign up

Export Citation Format

Share Document