Inhibition of�Rho‑kinase is involved in the therapeutic effects of atorvastatin in heart ischemia/reperfusion

Cheng, Chao; Liu, Xiaobo; Bi, Shao‐Jie; Lu, Qinghua; Zhang, Juan

doi:10.3892/etm.2020.9070

Cited by 7 publications

(7 citation statements)

References 42 publications

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“…In model rats, atorvastatin therapy significantly lowers plasma CK-MB and lactate dehydrogenase levels ( 28 ). Moreover, pretreatment with atorvastatin significantly reduces plasma IL-6 and TNF-α levels as well as Rho-kinase activity, myocardial infarct size, and cardiomyocyte apoptosis ( 29 ). Studies have shown that the intestinal microflora is altered during the development and treatment of various diseases, and participates in numerous physiological processes, including the inflammatory response, and energy and nutrient metabolism ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Jia-Wei-Si-Miao-Yong-An decoction modulates intestinal flora and metabolites in acute coronary syndrome model

Zhao

Wang

et al. 2023

Front. Cardiovasc. Med.

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AimsWe assessed the efficacy of the traditional Chinese medicine formulation Jia-Wei-Si-Miao-Yong-An decoction (HJ11) in the treatment of acute coronary syndrome and evaluated its impact on the intestinal microbiota and their metabolites.MethodsAn acute coronary syndrome model was established in rats, which were randomly assigned to the model, HJ11 treatment, and atorvastatin treatment groups. Rats were then administered saline solution (model and sham operation control groups) or drugs by oral gavage for 28 d. Echocardiography was performed and serum creatine kinase-MB and cardiac troponin I levels were monitored to examine the cardiac function. Inflammation was evaluated using hematoxylin and eosin staining of heart tissue, and serum interleukin-2, interleukin-6, tumor necrosis factor alpha, and high-sensitivity C-reactive protein measurements. Gut microbiota composition was analyzed via 16S rRNA gene sequencing. Metabolomics was used to determine fecal metabolites and elucidate the modes of action of HJ11 in acute coronary syndrome treatment.ResultsHJ11 improved cardiac function and attenuated inflammation in rats with acute coronary syndrome. Relative to the untreated model group, the HJ11-treated group presented normalized Firmicutes/Bacteroidetes ratio and reduced abundances of the bacterial genera norank_f__Ruminococcaceae, Desulfovibrio, Clostridium_sensu_stricto_1, Adlercreutzia, Staphylococcus, Bacteroides, Prevotella, Rikenellaceae_RC9_gut_group, unclassified_o__Bacteroidales, and Ruminococcus_gauvreauii_group. We found 23 differentially expressed intestinal metabolites, and the enriched metabolic pathways were mainly related to amino acid metabolism. We also discovered that asymmetric dimethylarginine levels were strongly associated with cardiovascular disease. Correlation analyses revealed strong associations among intestinal microflora, their metabolites, proinflammatory factors, and cardiac function. Hence, the therapeutic effects of HJ11 on acute coronary syndrome are related to specific alterations in gut microbiota and their metabolites.ConclusionThis work demonstrated that HJ11 effectively treats acute coronary syndrome. HJ11 seems to increase the abundance of beneficial bacterial taxa (Bacteroides and Rikenellaceae_RC9_gut_group), mitigate the risk factors associated with cardiovascular disease, alter bacterial metabolites, lower asymmetric dimethylarginine levels, and effectively treat acute coronary syndrome.

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Section: Discussionmentioning

confidence: 99%

Jia-Wei-Si-Miao-Yong-An decoction modulates intestinal flora and metabolites in acute coronary syndrome model

Zhao

Wang

et al. 2023

Front. Cardiovasc. Med.

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“…MDA is a widely used oxidant parameter in oxidative stress-induced LPO [22]. Actually, the studies have reported that atorvastatin inhibits MDA and proinflammatory cytokine production and protects heart tissue from ischemia-reperfusion injury [23]. Another experimental study designed with cadmium chloride, atorvastatin treatment prevented oxidative liver tissue damage [24].…”

Section: Discussionmentioning

confidence: 99%

Adenosine Triphosphate Exerts Cardioprotective Effect on High-Dose Atorvastatin-Induced Heart Damage in Rats

Coskun

2022

Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi

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Atorvastatin is a statin derivated hypolipidemic drug used in the treatment of hyperlipidemia. High-dose atorvastatin has been shown to significantly reduce adenosine triphosphate (ATP) levels in the heart tissue. Reduction of ATP by atorvastatin causes increased production of reactive oxygen species (ROS), decreased antioxidants, subsequent cell membrane and mitochondrial damage. The present study aimed to biochemically investigate the protective effect of ATP against possible cardiac damage caused by high dose atorvastatin in rats. Male Wistar rats were divided into atorvastatin (ATR), atorvastatin+ATP (AAT) and healthy control (HG) groups. ATP at a 25 mg/kg dose was injected intraperitoneally (ip) to the AAT (n-6) group. 0.9% NaCl as solvent was applied to the ATR (n-6) and HG (n-6) groups by the same route. Afterward, atorvastatin was administered orally at a dose of 20 mg/kg to the AAT and ATR groups. This procedure was repeated once daily for four weeks. At the end of this period, blood samples were taken into tubes to analyze troponin-I (TP-I) by cardiac puncture before animals were sacrificed with high-dose anesthesia. In addition, heart tissues were removed and malondialdehyde (MDA), total glutathione (tGSH), total oxidant (TOS) and total antioxidant (TAS) levels were measured. Biochemical test results showed that in the heart tissues of the ATR group, the oxidative parameters MDA and TOS significantly increased, while the antioxidant parameters tGSH and TAS significantly decreased compared to AAT and HG. Atorvastatin alone administration significantly increased blood TP-I levels, a marker of cardiac tissue damage. However, ATP administration to AAT group animals brought oxidative parameter levels closer to HG, despite high-dose atorvastatin treatment. In addition, the significant decrease in antioxidant levels was prevented by ATP application. High doses of atorvastatin can cause heart damage. ATP treatment was able to prevent atorvastatin-induced oxidative heart damage.

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“…CKD, chronic kidney disease; GDF- Statins induce eNOS upregulation (increase eNOS mRNA stability) and thereby increase NO bioavailability (Figure 2) [30]. This effect may be achieved through the inhibition of the Rho/ROCK pathway [31] and the activation of PI3K/protein kinase Akt pathway [31]. In endothelial cells, ROCKs inhibit the pro-survival PI3K/protein kinase Akt pathway, resulting in decreased eNOS expression and cGMP levels [32].…”

Section: Microcirculatory Endothelial Dysfunction In Hfpef and Endoth...mentioning

confidence: 99%

Use of Statins in Heart Failure with Preserved Ejection Fraction: Current Evidence and Perspectives

Ovchinnikov,

Potekhina,

Arefieva

et al. 2024

IJMS

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Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure (HF) with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties of statins, such as anti-inflammatory, antihypertrophic, antifibrotic, and antioxidant effects, are generally accepted and may be beneficial in HF, especially in HFpEF. Numerous observational clinical trials have consistently shown a beneficial prognostic effect of statins in patients with HFpEF, while the results of two larger trials in patients with HFrEF have been controversial. Such differences may be related to a more pronounced impact of the pleiotropic properties of statins on the pathophysiology of HFpEF and pro-inflammatory comorbidities (arterial hypertension, diabetes mellitus, obesity, chronic kidney disease) that are more common in HFpEF. This review discusses the potential mechanisms of statin action that may be beneficial for patients with HFpEF, as well as clinical trials that have evaluated the statin effects on left ventricular diastolic function and clinical outcomes in patients with HFpEF.

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Inhibition of�Rho‑kinase is involved in the therapeutic effects of atorvastatin in heart ischemia/reperfusion

Cited by 7 publications

References 42 publications

Jia-Wei-Si-Miao-Yong-An decoction modulates intestinal flora and metabolites in acute coronary syndrome model

Jia-Wei-Si-Miao-Yong-An decoction modulates intestinal flora and metabolites in acute coronary syndrome model

Adenosine Triphosphate Exerts Cardioprotective Effect on High-Dose Atorvastatin-Induced Heart Damage in Rats

Use of Statins in Heart Failure with Preserved Ejection Fraction: Current Evidence and Perspectives

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