Abstract 10898: The Probiotic Bacterium Lactobacillus Plantarum 299v Improves Vascular Endothelial Function and Decreases Inflammatory Biomarkers in Men With Established Cardiovascular Disease

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Mobin Malik ◽  
Michael E Widlansky ◽  
Tisha Suboc ◽  
Allison Coulliard ◽  
Jidong Su ◽  
...  

Introduction: There is a significant unmet clinical need to identify novel therapies to prevent and treat the progression of cardiovascular disease. This requires identification of additional contributory processes to the pathogenesis of heart disease so that mechanism-based interventions may be developed. Hypothesis: Our objective was to translate the recently discovered mechanistic link in rats between changes in the intestinal microbiota and the pathogenesis of cardiovascular disease to humans. Methods: Twenty male adult patients with stable coronary heart disease on stable doses of vasoactive medications and HMG-CoA reductase inhibitors consumed a probiotic drink containing Lactobacillus plantarum 299v (3 oz. serving containing 20 billion colony forming units) once a day for 42 days. Vascular endothelial function was measured at the beginning and end of the study period by brachial flow-mediated dilation. Results: The probiotic improved brachial artery flow mediated dilation, a surrogate marker of cardiovascular risk, by 33% from 3.55 + 1.96% to 4.73 + 2.33% with a trend towards decreased LDL-cholesterol by 8% from 96 + 11 mg/dl to 88 + 10 mg/dl. Probiotic therapy decreased circulating levels of the inflammatory cytokines IL-8 by 24% (17±2 to 13±1 pg/ml) and IL-12 by 20% (56±7 to 45±6 pg/ml). Whole microbiome analysis based on abundance of 2,206 taxa using hierarchical clustering revealed no separation of the overall intestinal microbial population between pre- and post-probiotic treatment samples. Bacterial genus richness ranged from 334 to 530 and archaeal ranged from 8 to 25, with no significant differences between pre- and post-probiotic samples. Lactobacillus and Bacillus species were enriched in post-probiotic samples. Lactobacillus plantarum 299v levels were elevated in post-probiotic samples, confirming patient compliance. Conclusions: Our discovery of a relationship between Lactobacillus plantarum 299v, improved vascular endothelial function and decreased inflammation indicates intestinal microbiota may be developed as therapies to prevent and treat the progression of cardiovascular disease.

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Kazuki Hotta ◽  
Wayne B Batchelor ◽  
James Graven ◽  
Vishal Dahya ◽  
Thomas E Noel ◽  
...  

Patients with peripheral artery disease (PAD) frequently have walking impairment due to lower extremity claudication. Our preliminary results in a rat model of aging indicate that a program of daily calf muscle stretching improves endothelium-dependent dilation of soleus muscle arterioles and increases soleus muscle blood flow during exercise. However, the effects of muscle stretching on the function of arteries supplying the legs of PAD patients is unknown. We hypothesized that daily calf muscle stretching improves vascular endothelial function and walking distance in PAD patients. To test our hypothesis, a randomized, non-blinded, crossover study was performed. Four weeks of muscle stretching (30 min/d, 5 days/wk) and 4 weeks of sedentary lifestyle (no stretching) were performed in random order. Thirteen patients with PAD participated in this study (71 ± 2 years old; 7 males and 6 females). During the stretching intervention both ankle joints were maintained at 15o of dorsiflexion using ankle dorsiflexion splints to stretch their calf muscles at home. Flow-mediated dilation (FMD; dilation to post-occlusion reactive hyperemia) and nitroglycerin-induced dilation (dilation to sublingual 0.4 mg nitroglycerin) of the popliteal artery were measured after 4 weeks of muscle stretching and after the no stretching period using ultrasound. A six-minute walk test was also performed to obtain walking distance. After 4 weeks of muscle stretching, FMD and 6-minute walking distance significantly improved as compared to the values measured after 4 weeks of no stretching (FMD: 5.2 ± 0.6 % vs. 3.7 ± 0.4 %, P=0.003 stretching vs. no stretching, 6-minute walking distance: 355 ± 32 m vs. 311 ± 31 m, P=0.007, stretching vs. no stretching; mean ± SE). No difference in nitroglycerin-induced dilation was found between groups (10.9 ± 1.4 vs. 9.9 ± 1.1 %, P=0.54, stretching vs. no stretching). Percentage change of walking distance (%change = [(stretching - no stretching) / no stretching] x 100) significantly correlated with the %change of FMD (R 2 =0.65, P=0.03). These results indicate that static calf muscle stretching enhances vascular endothelial function of the popliteal artery, contributing to improvement of walking tolerance in PAD patients.


2012 ◽  
Vol 02 (03) ◽  
pp. 338-345 ◽  
Author(s):  
Kazunari Suzuki ◽  
Kentaro Watanabe ◽  
Tatsuya Suzuki ◽  
Motoshi Ouchi ◽  
Shoko Futami-Suda ◽  
...  

2013 ◽  
Vol 25 (2) ◽  
pp. 222-227 ◽  
Author(s):  
Mohammad Reza Sabri ◽  
Hooman Daryoushi ◽  
Mojgan Gharipour

AbstractBackgroundRepairing cyanotic congenital heart disease may be associated with preserving endothelial function. The present study aimed to evaluate vascular endothelial function in patients with repaired cyanotic congenital heart disease.MethodsIn a case–control study conducted in 2012 in Isfahan, Iran, 42 consecutive patients aged <35 years who had suffered from different types of cyanotic congenital heart disease and had undergone complete repair of their congenital heart defect were assessed in regard to their endothelial function state by measuring flow-mediated dilatation and other cardiac function indices. They were paired with 42 sex- and age-matched healthy controls.ResultsThe mean flow-mediated dilatation was lower in patients with repaired cyanotic congenital heart disease than in the controls [6.14±2.78 versus 8.16±1.49 respectively (p<0.001)]. Significant adverse correlations were found between flow-mediated dilatation, age, and body mass indexes, in those who underwent repair surgery. In addition, flow-mediated dilatation had a positive association with the shortening fraction, ejection fraction, and tricuspid annular plane systolic excursion value, and it was also inversely associated with carotid intima-media thickness and the myocardial performance index. The mean of the flow-mediated dilatation was significantly higher in the group with tetralogy of Fallot along with complete repair before the age of 2.5 years and also in those patients with total anomalous pulmonary venous connection or transposition of the great arteries repaired with an arterial switch operation before 6 months of age, compared with the other two subgroups. This includes patients with a tetralogy of Fallot defect repaired after 4 years of age and those with complex cyanotic congenital heart disease that was repaired after 2.5 years of age (mean age at repair 9±6.1 years).ConclusionEarly repair of a cyanotic defect can result in the protection of vascular endothelial function and prevent the occurrence of vascular accidents at an older age.


2020 ◽  
Author(s):  
Yue-hong Shen ◽  
Shu-lin Wang ◽  
Na Wu ◽  
Yu-chen Dai ◽  
Qian Zhou ◽  
...  

Abstract ObjectiveOur study aimed to investigate the potential mechanisms of the herb pair Zhizi-Danshen (ZD) for coronary heart disease (CHD) using network pharmacological data mining technology.MethodsThe Traditional Chinese Medicine System Pharmacology (TCMSP) database was used to collect the active ingredients of ZD and predict ZD-related target proteins. Afterwards, we identified CHD-related targets from DisGeNET database, NCBI gene database, and TTD database. The common targets both from ZD and CHD were screened by Venny2.1, which were then imported into the String database for protein-protein interaction (PPI) analysis. Finally, the GO and KEGG enrichment analysis were performed by R software, and the network construction was established using Cytoscape3.7.2.ResultsWe obtained 199 possible targets from 62 candidate ingredients of ZD and 1033 CHD-ralated targets, with 83 overlapping common target genes. Then, 11 core targets were acquired from PPI network analysis. Further, GO analysis showed that these common targets mainly influenced receptor ligand activity,cytokine activity,cytokine receptor binding,steroid hormone receptor activity, and peptide binding. KEGG pathway analysis indicated that ZD affected CHD through seven important pathways linked to vascular endothelial function regulation (fluid shear stress and atherosclerosis,AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway), imflammatory effects (IL-17 signaling pathway, TNF signaling pathway,Toll-like receptor signaling pathway),and hormone regulation (relaxin signaling pathway). ConclusionsThis study revealed the potential pharmacological mechanisms of ZD against CHD, which were mainly associated with regulation of vascular endothelial function and inflammatory effects, promotion of vasodilatation, and prevention of cardiac fibrosis. Moreover, it provided a novel conception for the development of alternative therapies on CHD.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Fei Li ◽  
Jialin Duan ◽  
Meina Zhao ◽  
Shaojie Huang ◽  
Fei Mu ◽  
...  

AbstractSalvia miltiorrhiza-Dalbergia odorifera coupled-herbs (SMDOCH) has been used to treat coronary heart disease (CHD) for thousands of years, but its unclear bioactive components and mechanisms greatly limit its clinical application. In this study, for the first time, we used network pharmacology to elucidate the mechanisms of action of SMDOCH on CHD. We collected 270 SMDOCH-related targets from 74 bioactive components and 375 CHD-related targets, with 58 overlapping common targets. Next, we performed enrichment analysis for common-target network and protein-protein interaction (PPI) network. The results showed that SMDOCH affected CHD mainly through 10 significant signaling pathways in three biological processes: ‘vascular endothelial function regulation’, ‘inflammatory response’, and ‘lipid metabolism’. Six pathways belonged to the ‘vascular endothelial function regulation’ model, which primarily regulated hormone (renin, angiotensin, oestrogen) activity, and included three key upstream pathways that influence vascular endothelial function, namely KEGG:04933, KEGG:05418, and KEGG:04066. Three pathways, namely KEGG:04668, KEGG:04064, and KEGG:04620, belonged to the ‘inflammatory response’ model. One pathway (KEGG:04920) belonged to the ‘lipid metabolism’ model. To some extent, this study revealed the potential bioactive components and pharmacological mechanisms of SMDOCH on CHD, and provided a new direction for the development of new drugs for the treatment of CHD.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nandu Goswami ◽  
Per Morten Fredriksen ◽  
Knut E. A. Lundin ◽  
Chidozie Agu ◽  
Simiat Olanike Elias ◽  
...  

Abstract Background COVID-19 has affected almost every country in the world, especially in terms of health system capacity and economic burden. People from sub-Saharan Africa (SSA) often face interaction between human immunodeficiency virus (HIV) infection and non-communicable diseases such as cardiovascular disease. Role of HIV infection and anti-retroviral treatment (ART) in altered cardiovascular risk is questionable and there is still need to further carry out research in this field. However, thus far it is unclear, what impact the COVID-19 co-infection in people living with HIV (PLHIV), with or without therapy will have. The ENDOCOVID project aims to investigate whether and how HIV-infection in COVID-19 patients modulates the time course of the disease, alters cardiovascular risk, and changes vascular endothelial function and coagulation parameters/ thrombosis risk. Methods A total of 1026 patients will be included into this study. Cardiovascular research PLHIV with (n = 114 in each of the three recruiting centers) - or without - ART (n = 114 in each of the three recruiting centers) with COVID-19 and HIV-negative with COVID-19 (n = 114 in each of the three recruiting centers) will be carried out via clinical and biochemical measurements for cardiovascular risk factors and biomarkers of cardiovascular disease (CVD). Vascular and endothelial function will be measured by brachial artery flow-mediated dilatation (FMD), carotid intima-media thickness (IMT) assessments, and retinal blood vessel analyses, along with vascular endothelial biomarkers and cogualation markers. The correlation between HIV-infection in COVID-19 PLHIV with or without ART and its role in enhancement of cardiovascular risk and endothelial dysfunction will be assessed at admission, weekly, at discharge and, 4 weeks post-discharge (if possible). Impact of project The ENDOCOVID project aims to evaluate in the long-term the cardiovascular risk and vascular endothelial function in PLHIV thus revealing an important transitional cardiovascular phenotype in COVID-19. The study was registered under clinicaltrials.gov (NCT04709302).


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