scholarly journals Gut microbiota from coronary artery disease patients contributes to vascular dysfunction in mice by regulating bile acid metabolism and immune activation

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Honghong Liu ◽  
Ran Tian ◽  
Hui Wang ◽  
Siqin Feng ◽  
Hanyu Li ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Arterial Stiffness ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Bile Acid Metabolism ◽  
Clostridium Symbiosum ◽  
Artery Disease

Abstract Background The gut microbiota was shown to play a crucial role in the development of vascular dysfunction, and the bacterial composition differed between healthy controls and coronary artery disease patients. The goal of this study was to investigate how the gut microbiota affects host metabolic homeostasis at the organism scale. Methods We colonized germ-free C57BL/6 J mice with faeces from healthy control donors (Con) and coronary artery disease (CAD) patients and fed both groups a high fat diet for 12 weeks. We monitored cholesterol and vascular function in the transplanted mice. We analysed bile acids profiles and gut microbiota composition. Transcriptome sequencing and flow cytometry were performed to evaluate inflammatory and immune response. Results CAD mice showed increased reactive oxygen species generation and intensive arterial stiffness. Microbiota profiles in recipient mice clustered according to the microbiota structure of the human donors. Clostridium symbiosum and Eggerthella colonization from CAD patients modulated the secondary bile acids pool, leading to an increase in lithocholic acid and keto-derivatives. Subsequently, bile acids imbalance in the CAD mice inhibited hepatic bile acids synthesis and resulted in elevated circulatory cholesterol. Moreover, the faecal microbiota from the CAD patients caused a significant induction of abnormal immune responses at both the transcriptome level and through the enhanced secretion of cytokines. In addition, microbes belonging to CAD promoted intestinal inflammation by contributing to lamina propria Th17/Treg imbalance and worsened gut barrier permeability. Conclusions In summary, our findings elucidated that the gut microbiota impacts cholesterol homeostasis by modulating bile acids. In addition, the CAD-associated bacterial community was shown to function as an important regulator of systemic inflammation and to influence arterial stiffness.

scholarly journals Prognostic value of coronary vascular dysfunction assessed by rubidium-82 PET/CT imaging in patients with resistant hypertension without overt coronary artery disease

2021 ◽  
Author(s):  
Valeria Gaudieri ◽  
Teresa Mannarino ◽  
Emilia Zampella ◽  
Roberta Assante ◽  
Adriana D’Antonio ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Myocardial Perfusion ◽  
Risk Stratification ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Left Ventricular ◽  
Pet Ct ◽  
Artery Disease ◽  
Rubidium 82

Abstract Purpose The identification of coronary vascular dysfunction may enhance risk stratification in patients with resistant hypertension (RH). We evaluated if impaired coronary vascular function, assessed by rubidium-82 (82Rb) positron emission tomography/computed tomography (PET/CT) imaging, is associated with increased cardiovascular risk in patients with hypertension without overt coronary artery disease (CAD). Methods We studied 517 hypertensive subjects, 26% with RH, without overt CAD, and with normal stress-rest myocardial perfusion imaging at 82Rb PET/CT. The outcome end points were cardiac death, nonfatal myocardial infarction, coronary revascularization, and admission for heart failure. Results Over a median of 38 months (interquartile range 26 to 50), 21 cardiac events (4.1% cumulative event rate) occurred. Patients with RH were older (p < 0.05) and had a higher prevalence of left ventricular hypertrophy (p < 0.001), a lower hyperemic myocardial blood flow (MBF), and myocardial perfusion reserve (MPR) (both p < 0.001) compared to those without. Conversely, coronary artery calcium content and baseline MBF were not different between patients with and without RH. At univariable Cox regression analysis, age, RH, left ventricular ejection fraction, coronary artery calcium score, and reduced MPR were significant predictors of events. At multivariable analysis, age, RH, and reduced MPR (all p < 0.05) were independent predictors of events. Patients with RH and reduced MPR had the highest risk of events and the major risk acceleration over time. Conclusion The findings suggest that the assessment of coronary vascular function may enhance risk stratification in patients with hypertension.

scholarly journals Prognostic Value of Coronary Vascular Dysfunction Assessed by Rubidium-82 PET/CT Imaging in Patients With Resistant Hypertension Without Overt Coronary Artery Disease

2021 ◽  
Author(s):  
Valeria Gaudieri ◽  
Teresa Mannarino ◽  
Emilia Zampella ◽  
Roberta Assante ◽  
Adriana D’Antonio ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Myocardial Perfusion ◽  
Risk Stratification ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Left Ventricular ◽  
Pet Ct ◽  
Artery Disease ◽  
Rubidium 82

Abstract PurposeThe identification of coronary vascular dysfunction may enhance risk stratification in patients with resistant hypertension (RH). We evaluated if impaired coronary vascular function, assessed by rubidium-82 (82Rb) positron emission tomography/computed tomography (PET/CT) imaging, is associated with increased cardiovascular risk in patients with hypertension without overt coronary artery disease (CAD).MethodsWe studied 517 hypertensive subjects, 26% with RH, without overt CAD and with normal stress-rest myocardial perfusion imaging at 82Rb PET/CT. The outcome end points were cardiac death, nonfatal myocardial infarction, coronary revascularization, and admission for heart failure.ResultsOver a median of 38 months (interquartile range 26 to 50), 21 cardiac events (4.1% cumulative event rate) occurred. Patients with RH were older (p < 0.05), had a higher prevalence of left ventricular hypertrophy (p < 0.001), a lower hyperemic myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) (both p < 0.001) compared to those without. Conversely, coronary artery calcium content and baseline MBF were not different between patients with and without RH. At univariable Cox regression analysis, age, RH, left ventricular ejection fraction, coronary artery calcium score, and reduced MPR were significant predictors of events. At multivariable analysis, age, RH, and reduced MPR (all p < 0.05) were independent predictors of events. Patients with RH and reduced MPR had the highest risk of events and the major risk acceleration over time.ConclusionThe findings suggest that the assessment of coronary vascular function may enhance risk stratification in patients with hypertension.

Abstract P188: “False Positive” Stress Testing: Does Endothelial Vascular Dysfunction Explain ST-Segment Depression in the Absence of Clinical Coronary Artery Disease in Women?

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Shilpa Agrawal ◽  
Puja Mehta ◽  
Tara Sedlak ◽  
Zachary Hobel ◽  
Chrisandra Shufelt ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
False Positive ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Reactive Hyperemia ◽  
St Depression ◽  
St Segment ◽  
Artery Disease ◽  
Asymptomatic Women

Background: Current guidelines do not endorse exercise electrocardiography (Ex-ECG) screening in asymptomatic adults due to poor diagnostic accuracy for clinical coronary artery disease (CAD), however Ex-ECG combined with other variables paradoxically has strong prognostic accuracy for cardiovascular mortality. Ex-ECG ST segment depression “false positive” results are common in women, who have higher rates of vascular dysfunction such as Raynaud’s and migraines compared to men. We hypothesized that ST segment depression indicates endothelial vascular dysfunction, which is known to predict an adverse prognosis. To test this hypothesis, we evaluated the relationship between Ex-ECG and peripheral endothelial vascular function in asymptomatic women. Methods: Asymptomatic women with no cardiac risk factors and normal resting ECG underwent maximal Bruce protocol Ex-ECG testing (GE Healthcare). Computer-generated Ex-ECG ST segment values were independently verified by 2 cardiologists. Based on established methods, endothelial vascular function was assessed by calculating reactive hyperemia index (RHI) using peripheral vascular testing (Endopat, Itamar). As established previously, RHI <1.68 is abnormal and indicates endothelial vascular dysfunction. Results: Among 35 women, mean age 54±8 years and BMI 24±4, there were 5 (14%) women with abnormal RHI. Women with abnormal RHI had a greater (more abnormal) ST/HR slope, a trend toward greater peak ST depression, and achieved lower METs than women with normal RHI (Table 1). Conclusion: Among asymptomatic women, endothelial vascular dysfunction was associated with abnormal Ex-ECG results characterized by greater ST/HR slope, greater ST depression, and lower exercise capacity. These findings suggest that “false positive” ST-segment depression in the absence of clinical CAD in women may be explained by endothelial vascular dysfunction. Our study further suggests that endothelial vascular dysfunction may explain the Ex-ECG diagnostic/prognostic paradox.

Osteoprotegerin and Osteopontin Serum Levels are Associated with Vascular Function and Inflammation in Coronary Artery Disease Patients

2020 ◽  
Vol 18 (5) ◽  
pp. 523-530 ◽  
Author(s):  
Konstantinos Maniatis ◽  
Gerasimos Siasos ◽  
Evangelos Oikonomou ◽  
Manolis Vavuranakis ◽  
Marina Zaromytidou ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Function ◽  
Vascular Function ◽  
Serum Levels ◽  
Atherosclerosis Progression ◽  
Control Subjects ◽  
Significant Difference ◽  
Artery Disease ◽  
Stable Cad

Background: Osteoprotegerin and osteopontin have recently emerged as key factors in both vascular remodelling and atherosclerosis progression. Interleukin-6 (IL-6) is an inflammatory cytokine with a key role in atherosclerosis. The relationship of osteoprotegerin, osteopontin, and IL-6 serum levels with endothelial function and arterial stiffness was evaluated in patients with coronary artery disease (CAD). Methods: We enrolled 219 patients with stable CAD and 112 control subjects. Osteoprotegerin, osteopontin and IL-6 serum levels were measured using an ELISA assay. Endothelial function was evaluated by flow-mediated dilation (FMD) in the brachial artery and carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. Results: There was no significant difference between control subjects and CAD patients according to age and sex. Compared with control subjects, CAD patients had significantly impaired FMD (p<0.001) and increased PWV (p=0.009). CAD patients also had significantly higher levels of osteoprotegerin (p<0.001), osteopontin (p<0.001) and IL-6 (p=0.03), compared with control subjects. Moreover, IL-6 levels were correlated with osteoprotegerin (r=0.17, p=0.01) and osteopontin (r=0.30, p<0.001) levels. FMD was correlated with osteoprotegerin levels independent of possible confounders [b coefficient= - 0.79, 95% CI (-1.54, -0.05), p=0.04]. Conclusion: CAD patients have increased osteoprotegerin, osteopontin and IL-6 levels. Moreover, there is a consistent association between osteoprotegerin and osteopontin serum levels, vascular function and inflammation in CAD patients. These findings suggest another possible mechanism linking osteoprotegerin and osteopontin serum levels with CAD progression through arterial wall stiffening and inflammation.

scholarly journals Association of Arterial Stiffness with Serum Bilirubin Levels in Established Coronary Artery Disease

2012 ◽  
Vol 51 (16) ◽  
pp. 2083-2089 ◽  
Author(s):  
Cansheng Zhu ◽  
Zhaojun Xiong ◽  
Zhenda Zheng ◽  
Yanming Chen ◽  
Xiaohong Chen ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Arterial Stiffness ◽  
Serum Bilirubin ◽  
Established Coronary Artery Disease ◽  
Artery Disease

P1.12PROGNOSTIC ROLE OF REVERSIBLE ARTERIAL STIFFNESS IN MEN WITH CORONARY ARTERY DISEASE

2009 ◽  
Vol 3 (4) ◽  
pp. 163
Author(s):  
I.A. Orlova ◽  
E. Nuraliev ◽  
G. Makarova ◽  
E. Yarovaya ◽  
F.T. Ageev
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Arterial Stiffness ◽  
Artery Disease

scholarly journals Effects of Monotherapy with Clopidogrel vs. Aspirin on Vascular Function and Hemostatic Measurements in Patients with Coronary Artery Disease: The Prospective, Crossover I-LOVE-MONO Trial

2021 ◽  
Vol 10 (12) ◽  
pp. 2720
Author(s):  
Hyun-Woong Park ◽  
Min-Gyu Kang ◽  
Jong-Hwa Ahn ◽  
Jae-Seok Bae ◽  
Udaya S. Tantry ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Function ◽  
Vascular Function ◽  
Platelet Reactivity ◽  
Reactive Hyperemia ◽  
Open Label ◽  
Peripheral Arterial Tonometry ◽  
Coagulation Activity ◽  
Artery Disease

To evaluate the effect of clopidogrel vs. aspirin monotherapy on vascular function and hemostatic measurement. Background: Monotherapy with P2Y12 receptor inhibitor vs. aspirin can be a useful alterative to optimize clinical efficacy and safety in high-risk patients with coronary artery disease (CAD). Methods: We performed a randomized, open-label, two-period crossover study in stented patients receiving at least 6-month of dual antiplatelet therapy (DAPT). Thirty CAD patients with moderate-to-high ischemic risk were randomly assigned to receive either 75 mg of clopidogrel or 100 mg of aspirin daily for 4 weeks, and were crossed over to the other strategy for 4 weeks. Vascular function was evaluated with reactive hyperemia-peripheral arterial tonometry (RH-PAT) and brachial-ankle pulse wave velocity (baPWV). Hemostatic profiles were measured with VerifyNow and thromboelastography (TEG). The primary endpoint was the reactive hyperemia index (RHI) during clopidogrel or aspirin monotherapy. Results: Clopidogrel vs. aspirin monotherapy was associated with better endothelial function (RHI: 2.11 ± 0.77% vs. 1.87 ± 0.72%, p = 0.045), lower platelet reactivity (130 ± 64 vs. 214 ± 50 P2Y12 reaction unit [PRU], p < 0.001) and prolonged reaction time (TEG R: 5.5 ± 1.2 vs. 5.1 ± 1.1 min, p = 0.037). In multivariate analysis, normal endothelial function (RHI ≥ 2.1) was significantly associated with clot kinetics (TEG angle ≤ 68 degree) and ‘PRU ≤ 132’. ‘PRU ≤ 132’ was achieved in 46.2% vs. 3.8% during clopidogrel administration vs. aspirin monotherapy (odds ratio 21.4, 95% confidence interval 2.7 to 170.1, p < 0.001). Conclusions: In CAD patients, clopidogrel vs. aspirin monotherapy was associated with better endothelial function, greater platelet inhibition and lower coagulation activity, suggesting pleiotropic effects of clopidogrel on endothelial function and hemostatic profiles.

Sign in / Sign up

Export Citation Format

Share Document