Clock genes in hypertension

Richards, Jacob; Diaz, Alexander N.; Gumz, Michelle L.

doi:10.1097/mbp.0000000000000060

Cited by 67 publications

(38 citation statements)

References 58 publications

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“…This is consistent with our fundamental hypothesis, which was based on the recent demonstration of a strong link between dietary fiber, the gut microbiota, and the pathogenesis of inflammatory diseases. 9,10 In our study, fiber and acetate also upregulated the regulation of circadian rhythm, which is supported by its role in BP, 33 and downregulated the renin-angiotensin system in the kidney and mitogen-activated protein kinase signaling in the heart.…”

Section: Discussionsupporting

confidence: 74%

High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice

et al. 2017

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Background: 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. Methods: Gut microbiome, cardiorenal structure/function, and blood pressure were examined in sham and mineralocorticoid excess–treated mice with a control diet, high-fiber diet, or acetate supplementation. We also determined the renal and cardiac transcriptome of mice treated with the different diets. Results: We found that high consumption of fiber modified the gut microbiota populations and increased the abundance of acetate-producing bacteria independently of mineralocorticoid excess. Both fiber and acetate decreased gut dysbiosis, measured by the ratio of Firmicutes to Bacteroidetes, and increased the prevalence of Bacteroides acidifaciens . Compared with mineralocorticoid-excess mice fed a control diet, both high-fiber diet and acetate supplementation significantly reduced systolic and diastolic blood pressures, cardiac fibrosis, and left ventricular hypertrophy. Acetate had similar effects and markedly reduced renal fibrosis. Transcriptome analyses showed that the protective effects of high fiber and acetate were accompanied by the downregulation of cardiac and renal Egr1 , a master cardiovascular regulator involved in cardiac hypertrophy, cardiorenal fibrosis, and inflammation. We also observed the upregulation of a network of genes involved in circadian rhythm in both tissues and downregulation of the renin-angiotensin system in the kidney and mitogen-activated protein kinase signaling in the heart. Conclusions: A diet high in fiber led to changes in the gut microbiota that played a protective role in the development of cardiovascular disease. The favorable effects of fiber may be explained by the generation and distribution of one of the main metabolites of the gut microbiota, the short-chain fatty acid acetate. Acetate effected several molecular changes associated with improved cardiovascular health and function.

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Section: Discussionsupporting

confidence: 74%

High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice

et al. 2017

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“…Every clock gene KO mouse that has been tested exhibits a BP phenotype (Richards et al, 2014a). Global Bmal1 KO mice lose circadian rhythmicity of BP and are hypotensive (Curtis et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Desoxycorticosterone pivalate‐salt treatment leads to non‐dipping hypertension in Per1 knockout mice

et al. 2016

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Aim Increasing evidence demonstrates that circadian clock proteins are important regulators of physiological functions including blood pressure. An established risk factor for developing cardiovascular disease is the absence of a blood pressure dip during the inactive period. The goal of the present study was to determine the effects of a high salt diet plus mineralocorticoid on PER1-mediated blood pressure regulation in a salt-resistant, normotensive mouse model, C57BL/6J. Methods Blood pressure was measured using radiotelemetry. After control diet, wild type and Per1 knockout mice were given a high salt diet (4% NaCl) and the long-acting mineralocorticoid deoxycorticosterone pivalate. Blood pressure and activity rhythms were analyzed to evaluate changes over time. Results Blood pressure in wild type mice was not affected by a high salt diet plus mineralocorticoid. In contrast, Per1 knockout mice exhibited significantly increased mean arterial pressure in response to a high salt diet plus mineralocorticoid. The inactive/active phase ratio of mean arterial pressure in wild type mice was unchanged by high salt plus mineralocorticoid treatment. Importantly, this treatment caused Per1 knockout mice to lose the expected decrease or “dip” in blood pressure during the inactive compared to the active phase. Conclusion Loss of PER1 increased sensitivity to the high salt plus mineralocorticoid treatment. Italso resulted in a non-dipper phenotype in this model of salt-sensitive hypertension and provides a unique model of non-dipping. Together these data support an important role for the circadian clock protein PER1 in the modulation of blood pressure in a high salt/mineralocorticoid model of hypertension.

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“…27 Four major circadian genes have been identified: CLOCK, BMAL1, Period (per), and Cryptochrome (Cry). 27, 28 Given the extensive genotyping of the JHS cohort, including whole genome sequencing, investigating whether these genes contribute to non-dipping blood pressure and nocturnal hypertension could be conducted.…”

Section: Measurement Of Blood Pressure and Cardiovascular Parametersmentioning

confidence: 99%

Hypertension in Blacks

et al. 2017

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Clock genes in hypertension

Cited by 67 publications

References 58 publications

High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice

High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice

Desoxycorticosterone pivalate‐salt treatment leads to non‐dipping hypertension in Per1 knockout mice

Hypertension in Blacks

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