Probiotic Administration Attenuates Myocardial Hypertrophy and Heart Failure After Myocardial Infarction in the Rat

Gan, Xiaohong Tracey; Ettinger, Grace; Huang, Cathy; Burton, Jeremy P.; Haist, James V.; Rajapurohitam, Venkatesh; Sidaway, James E.; Martin, Glynn; Gloor, Gregory B.; Swann, Jonathan R.; Reid, Gregor; Karmazyn, Morris

doi:10.1161/circheartfailure.113.000978

Cited by 247 publications

(197 citation statements)

References 37 publications

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“…After 6 weeks of daily probiotic administration and sustained coronary artery ligation there was a significant attenuation of several indices of heart failure, including cardiac hypertrophy and ventricular remodeling. 117 Cardiac mechanical function was also maintained at normal levels whereas mechanical function significantly deteriorated in animals on placebo treatment over the course of 6 weeks. Cecum digesta microbial analysis using 16 S rRNA next-generation sequencing indicated no significant community-level changes in the microbiota.…”

Section: Application Of Probioticsmentioning

confidence: 94%

The influence of the human microbiome and probiotics on cardiovascular health

et al. 2014

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Section: Application Of Probioticsmentioning

confidence: 94%

The influence of the human microbiome and probiotics on cardiovascular health

et al. 2014

Self Cite

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“…The MI model was induced as described previously [19]. Briefly, the rats were anesthetized with intraperitoneal sodium pentobarbital (50 mg/kg), intubated, and then artificially ventilated with a rodent ventilator.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-223 Regulates Cardiac Fibrosis After Myocardial Infarction by Targeting RASA1

Liu¹,

Xu²,

Deng³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Percutaneous coronary intervention reduces acute myocardial infarction (MI)-induced mortality to a great extent, but effective treatments for MI-induced cardiac fibrosis and heart failure are still lacking. MicroRNAs (miRNAs) play a variety of roles in cells and have thus been investigated extensively. MicroRNA-223 (miR-223) expression has been reported to be altered in post-MI heart failure in humans; however, the roles of miR-223 in MI remain unknown. Our study aimed to elucidate the roles of miR-223 in cardiac fibrosis. Methods: Cultured cardiac fibroblasts (CFs) were activated by TGF-β1 stimulation. Gain and loss of miR-223 and RAS p21 protein activator 1 (RASA1) knockdown in CFs were achieved by transfecting the cells with miR-223 mimics and inhibitors, as well as small interfering RNA-RASA1 (siRASA1), respectively. Quantitative real-time reverse transcriptase-polymerase chain reactions (qRT-PCR) was used to determine miR-223-3p and RASA1 expression levels, and Cell Counting Kit-8 (CCK-8), transwell migration and scratch assays were performed to assess CFs viability and migration, respectively. Western blotting was used to detect collagen I, collagen III, alpha-smooth muscle actin (a-SMA), RASA1, p-Akt/t-Akt, p-MEK1/2/t-MEK1/2, and p-ERK1/2/t-ERK1/2 protein expressions, and immunofluorescence assays were used to detect the expression of α-actin, vimentin and α-SMA. Luciferase assays were carried out to determine whether miR-223 binds to RASA1. Rat models of MI were established by the ligation of the left anterior descending (LAD) coronary artery. MiR-223 inhibition in vivo was achieved via intramyocardial injections of the miR-223 sponge carried by adeno-associated virus 9 (AAV9). The cardiac function was detected by echocardiography, and cardiac fibrosis was shown by Masson’s trichrome staining. Results: miR-223 was increased in CFs compared to cardiomypcytes, and TGF-β1 treatment increased miR-223 expression in CFs. The miR-223 mimics enhanced cell proliferation and migration and collagen I, collagen III, and α-SMA protein expression in CFs, while the miR-223 inhibitors had contrasting effects and partially prevented the promoting effects of TGF-β1. qRT-PCR and western blotting revealed that miR-223 negatively regulated RASA1 expression, and the luciferase assays showed that miR-223 suppressed the luciferase activity of the RASA1 3’ untranslated region (3'UTR), indicating that miR-223 binds directly to RASA1. Similar to transfection with the miR-223 mimics, RASA1 knockdown enhanced cell proliferation and migration and collagen I, collagen III, and α-SMA protein expression in CFs. Moreover, RASA1 knockdown partially reversed the inhibitory effects of the miR-223 inhibitor on cell proliferation and migration and collagen I, collagen III, and α-SMA protein expression, indicating that the effects of miR-223 in CFs are partially mediated by the regulation of RASA1 expression. Further exploration showed that miR-223 mimics and siRASA1 promoted MEK1/2, ERK1/2 and AKT phosphorylation, while the mi...

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“…For example, some probiotics display cholesterollowering properties [43,44], improve atherosclerosis [45,46], or attenuate myocardial hypertrophy and heart failure after myocardial infarction [47].…”

Section: Probiotics In Hypertensionmentioning

confidence: 99%

Antihypertensive Effects of Probiotics

et al. 2017

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Gut dysbiosis in hypertension is characterized by (i) the gut microbioma that is less diverse and less rich with an increased Firmicutes/Bacteroidetes ratio and (ii) a decrease in acetate- and butyrate-producing bacteria and an increase in lactate-producing bacterial populations. The meta-analysis of the human studies supports that supplementation with probiotics reduces blood pressure. The mechanism of this antihypertensive effect of probiotics and its protective effect on endothelial function has not been fully elucidated. Further investigations are needed to clarify if the effects of probiotic bacteria result from the changes in the gut microbiota and its metabolic by-products; the restoration of the gut barrier function; and the effects on endotoxemia, inflammation, and renal sympathetic nerve activity.

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Probiotic Administration Attenuates Myocardial Hypertrophy and Heart Failure After Myocardial Infarction in the Rat

Cited by 247 publications

References 37 publications

The influence of the human microbiome and probiotics on cardiovascular health

The influence of the human microbiome and probiotics on cardiovascular health

MicroRNA-223 Regulates Cardiac Fibrosis After Myocardial Infarction by Targeting RASA1

Antihypertensive Effects of Probiotics

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