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      Implication of Gut Microbiota in Cardiovascular Diseases

      1 , 2 , 1 , 2 , 2 , 1 , 1
      Oxidative Medicine and Cellular Longevity
      Hindawi Limited

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          Abstract

          Emerging evidence has identified the association between gut microbiota and various diseases, including cardiovascular diseases (CVDs). Altered intestinal flora composition has been described in detail in CVDs, such as hypertension, atherosclerosis, myocardial infarction, heart failure, and arrhythmia. In contrast, the importance of fermentation metabolites, such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and secondary bile acid (BA), has also been implicated in CVD development, prevention, treatment, and prognosis. The potential mechanisms are conventionally thought to involve immune regulation, host energy metabolism, and oxidative stress. However, numerous types of programmed cell death, including apoptosis, autophagy, pyroptosis, ferroptosis, and clockophagy, also serve as a key link in microbiome-host cross talk. In this review, we introduced and summarized the results from recent studies dealing with the relationship between gut microbiota and cardiac disorders, highlighting the role of programmed cell death. We hope to shed light on microbiota-targeted therapeutic strategies in CVD management.

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          Most cited references94

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          Short-Chain Fatty Acids Protect Against High-Fat Diet-Induced Obesity via a PPARγ-Dependent Switch From Lipogenesis to Fat Oxidation.

          Short-chain fatty acids (SCFAs) are the main products of dietary fiber fermentation and are believed to drive the fiber-related prevention of the metabolic syndrome. Here we show that dietary SCFAs induce a peroxisome proliferator-activated receptor-γ (PPARγ)-dependent switch from lipid synthesis to utilization. Dietary SCFA supplementation prevented and reversed high-fat diet-induced metabolic abnormalities in mice by decreasing PPARγ expression and activity. This increased the expression of mitochondrial uncoupling protein 2 and raised the AMP-to-ATP ratio, thereby stimulating oxidative metabolism in liver and adipose tissue via AMPK. The SCFA-induced reduction in body weight and stimulation of insulin sensitivity were absent in mice with adipose-specific disruption of PPARγ. Similarly, SCFA-induced reduction of hepatic steatosis was absent in mice lacking hepatic PPARγ. These results demonstrate that adipose and hepatic PPARγ are critical mediators of the beneficial effects of SCFAs on the metabolic syndrome, with clearly distinct and complementary roles. Our findings indicate that SCFAs may be used therapeutically as cheap and selective PPARγ modulators.
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            High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice.

            Dietary intake of fruit and vegetables is associated with lower incidence of hypertension, but the mechanisms involved have not been elucidated. Here, we evaluated the effect of a high-fiber diet and supplementation with the short-chain fatty acid acetate on the gut microbiota and the prevention of cardiovascular disease.
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              Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation.

              Olfactory receptors are G protein-coupled receptors that mediate olfactory chemosensation and serve as chemosensors in other tissues. We find that Olfr78, an olfactory receptor expressed in the kidney, responds to short chain fatty acids (SCFAs). Olfr78 is expressed in the renal juxtaglomerular apparatus, where it mediates renin secretion in response to SCFAs. In addition, both Olfr78 and G protein-coupled receptor 41 (Gpr41), another SCFA receptor, are expressed in smooth muscle cells of small resistance vessels. Propionate, a SCFA shown to induce vasodilation ex vivo, produces an acute hypotensive response in wild-type mice. This effect is differentially modulated by disruption of Olfr78 and Gpr41 expression. SCFAs are end products of fermentation by the gut microbiota and are absorbed into the circulation. Antibiotic treatment reduces the biomass of the gut microbiota and elevates blood pressure in Olfr78 knockout mice. We conclude that SCFAs produced by the gut microbiota modulate blood pressure via Olfr78 and Gpr41.
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                Author and article information

                Contributors
                Journal
                Oxidative Medicine and Cellular Longevity
                Oxidative Medicine and Cellular Longevity
                Hindawi Limited
                1942-0900
                1942-0994
                September 26 2020
                September 26 2020
                : 2020
                : 1-14
                Affiliations
                [1 ]Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
                [2 ]Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, China
                Article
                10.1155/2020/5394096
                10b17cfa-94de-4346-b1fc-b53e3b688a57
                © 2020

                http://creativecommons.org/licenses/by/4.0/

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