Impacts of a Specific Cyclooxygenase-2 Inhibitor on Pressure Overload–Induced Myocardial Hypertrophy in Rats

Xie, Zhixiang; Wang, Shu-Yin; Liang, Zijing; Zeng, Liangbo; Lai, Rongde; Zheng, Ye; Pinhu, Liao

doi:10.1532/hsf.1971

Cited by 4 publications

(3 citation statements)

References 21 publications

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“…Recently, our group (Duchatsch et al, 2020) revealed that the same low‐dose of DEX used in this present study (50 μg/kg) decreased relative wall tension, increased internal diameters (LVDD and LVSD), increased LV vessel density and reduced myocardial collagen deposition, which most likely contributed to improve systolic and diastolic function in SHR, however, in that study systolic and diastolic function were reduced in SHR compared with Wistar rats before DEX treatment. Because myocardial remodeling may be somewhat determined by an inflammatory process (Cohn et al, 2000; Nian et al, 2004; Xie et al, 2019; Zimmer et al, 2020) and SHR presents higher levels of interleukin‐6 (IL‐6) and TNF‐α in the myocardium, accompanied by fibrotic infiltration and collagen deposition (Silva et al, 2017; Yao et al, 2009; You et al, 2018), it is possible to consider that DEX, which is a potent anti‐inflammatory drug, could decrease these inflammatory cytokines and improve cardiac fibrosis and collagen deposition (Xia et al, 2007) as shown in this present study. In agreement, in this present study, DEX treatment reduced the relative wall tension, increased the LV systolic diameter, and reduced the myocardial collagen deposition area; even though these responses were not sufficient to improve systolic function in SHR.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats

Tardelli

Duchatsch

Herrera

et al. 2021

J of Applied Toxicology

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Dexamethasone (DEX)‐induced hypertension is observed in normotensive rats, but little is known about the effects of DEX on spontaneously hypertensive animals (SHR). This study aimed to evaluate the effects of DEX on hemodynamics, cardiac hypertrophy and arterial stiffness in normotensive and hypertensive rats. Wistar rats and SHR were treated with DEX (50 μg/kg s.c., 14 d) or saline. Pulse wave velocity (PWV), echocardiographic parameters, blood pressure (BP), autonomic modulation and histological analyses of heart and thoracic aorta were performed. SHR had higher BP compared with Wistar, associated with autonomic unbalance to the heart. Echocardiographic changes in SHR (vs. Wistar) were suggestive of cardiac remodeling: higher relative wall thickness (RWT, +28%) and left ventricle mass index (LVMI, +26%) and lower left ventricle systolic diameter (LVSD, −19%) and LV diastolic diameter (LVDD, −10%), with slightly systolic dysfunction and preserved diastolic dysfunction. Also, SHR had lower myocardial capillary density and similar collagen deposition area. PWV was higher in SHR due to higher aortic collagen deposition. DEX‐treated Wistar rats presented higher BP (~23%) and autonomic unbalance. DEX did not change cardiac structure in Wistar, but PWV (+21%) and aortic collagen deposition area (+21%) were higher compared with control. On the other side, DEX did not change BP or autonomic balance to the heart in SHR, but reduced RWT and LV collagen deposition area (−12% vs. SHRCT). In conclusion, the results suggest a differential effect of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats.

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Section: Discussionmentioning

confidence: 99%

Differential effects of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats

Tardelli

Duchatsch

Herrera

et al. 2021

J of Applied Toxicology

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“…In addition, palmitic acid, a saturated acid, can bind to TLR4 coreceptor MD2, induce inflammatory cytokines in cardiomyocytes, and is positively associated with incident heart failure [19][20][21]. Therefore, the downregulation of arachidonic acid, DPA, and DHA levels and the upregulation of palmitic acid and prostaglandins levels in myocardial tissue might induce inflammation in mice in the ACM group, which can further lead to fibrosis, myocardial remodeling, and cardiac dysfunction [22]. When heart function was affected, the mechanical stress on cardiomyocytes increased, which, in turn, led to increased BNP [23,24].…”

Section: Metabolism Of Fatty Acidsmentioning

confidence: 99%

A Pilot Metabolomic Study on Myocardial Injury Caused by Chronic Alcohol Consumption—Alcoholic Cardiomyopathy

et al. 2021

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Chronic alcohol consumption leads to myocardial injury, ventricle dilation, and cardiac dysfunction, which is defined as alcoholic cardiomyopathy (ACM). To explore the induced myocardial injury and underlying mechanism of ACM, the Liber-DeCarli liquid diet was used to establish an animal model of ACM and histopathology, echocardiography, molecular biology, and metabolomics were employed. Hematoxylin-eosin and Masson’s trichrome staining revealed disordered myocardial structure and local fibrosis in the ACM group. Echocardiography revealed thinning wall and dilation of the left ventricle and decreased cardiac function in the ACM group, with increased serum levels of brain natriuretic peptide (BNP) and expression of myocardial BNP mRNA measured through enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (PCR), respectively. Through metabolomic analysis of myocardium specimens, 297 differentially expressed metabolites were identified which were involved in KEGG pathways related to the biosynthesis of unsaturated fatty acids, vitamin digestion and absorption, oxidative phosphorylation, pentose phosphate, and purine and pyrimidine metabolism. The present study demonstrated chronic alcohol consumption caused disordered cardiomyocyte structure, thinning and dilation of the left ventricle, and decreased cardiac function. Metabolomic analysis of myocardium specimens and KEGG enrichment analysis further demonstrated that several differentially expressed metabolites and pathways were involved in the ACM group, which suggests potential causes of myocardial injury due to chronic alcohol exposure and provides insight for further research elucidating the underlying mechanisms of ACM.

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“…17,18) It is confirmed that aspirin can attenuate pressure overload-induced cardiac interstitial fibrosis in mice with transverse aortic constriction (TAC) by inhibiting p-Erk1/2 and p-Akt/β-catenin signaling pathways. 19) Celecoxib, as a specific COX inhibitor, modulates hypertrophic signaling and inhibits pressure overloadinduced cardiac dysfunction. 20) Our previous studies showed that aspirin and celecoxib ameliorate pressure overload-induced myocardial hypertrophy and improve cardiac dysfunction in rats.…”

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confidence: 99%

Aspirin and Celecoxib Regulate Notch1/Hes1 Pathway to Prevent Pressure Overload-Induced Myocardial Hypertrophy

Wei,

Lu,

Zhang

et al. 2024

Int. Heart J.

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This study aimed to investigate the molecular mechanisms underlying the protective effects of cyclooxygenase (cox) inhibitors against myocardial hypertrophy.Rat H9c2 cardiomyocytes were induced by mechanical stretching. SD rats underwent transverse aortic constriction to induce pressure overload myocardial hypertrophy. Rats were subjected to echocardiography and tail arterial pressure in 12W. qPCR and western blot were used to detect the expression of Notch-related signaling. The inflammatory factors were tested by ELISA in serum, heart tissue, and cell culture supernatant.Compared with control, levels of pro-inflammatory cytokines IL-6, TNF-α, and IL-1β were increased and anti-inflammatory cytokine IL-10 was reduced in myocardial tissues and serum of rat models. Levels of Notch1 and Hes1 were reduced in myocardial tissues. However, cox inhibitor treatment (aspirin and celecoxib), the improvement of exacerbated myocardial hypertrophy, fibrosis, dysfunction, and inflammation was parallel to the activation of Notch1/Hes1 pathway. Moreover, in vitro experiments showed that, in cardiomyocyte H9c2 cells, application of -20% mechanical stretching activated inflammatory mediators (IL-6, TNF-α, and IL-1β) and hypertrophic markers (ANP and BNP). Moreover, expression levels of Notch1 and Hes1 were decreased. These changes were effectively alleviated by aspirin and celecoxib.Cox inhibitors may protect heart from hypertrophy and inflammation possibly via the Notch1/Hes1 signaling pathway.

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Impacts of a Specific Cyclooxygenase-2 Inhibitor on Pressure Overload–Induced Myocardial Hypertrophy in Rats

Cited by 4 publications

References 21 publications

Differential effects of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats

Differential effects of dexamethasone on arterial stiffness, myocardial remodeling and blood pressure between normotensive and spontaneously hypertensive rats

A Pilot Metabolomic Study on Myocardial Injury Caused by Chronic Alcohol Consumption—Alcoholic Cardiomyopathy

Aspirin and Celecoxib Regulate Notch1/Hes1 Pathway to Prevent Pressure Overload-Induced Myocardial Hypertrophy

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