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Histone Deacetylase Inhibition Attenuates Aortic Remodeling in Rats under Pressure Overload.

ABSTRACT: The use of histone deacetylase (HDAC) inhibitor is a novel therapeutic strategy for cardiovascular disease. Studies have shown that many HDAC inhibitors have the ability to reduce the aortic remodeling in various animal models. We hypothesized that the HDAC inhibitor, MGCD0103 (MGCD), attenuates aortic remodeling in rats under pressure overload-induced by transverse aortic constriction (TAC). The aortic ring tension analysis was conducted using the thoracic aorta. Sections of the aorta were visualized after hematoxylin and eosin, trichrome, and Verhoeff-van Gieson staining, and immunohistochemistry. The expression of genes related to aortic remodeling (?SMA, Mmp2, and Mmp9) and angiotensin receptors (Agtr1 and Agtr2) was determined by quantitative real-time polymerase chain reaction. There was a significant decrease in relaxation of the aorta when treated with MGCD. Fibrosis of the aortic wall and expression of angiotensin receptors increased in TAC rats, which was attenuated by MGCD. These results indicate that MGCD, an HDAC inhibitor, attenuates aortic remodeling in rats with TAC-induced pressure overload rats and may serve as a potential therapeutic target of antiaortic remodeling in pressure overload-induced hypertension-related diseases.

SUBMITTER: Jung H

PROVIDER: S-EPMC7397417 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Histone Deacetylase Inhibition Attenuates Aortic Remodeling in Rats under Pressure Overload.

Jung Hanna H Lee Eunjo E Kim Inkyeom I Kim Gun Jik GJ

BioMed research international 20200724

The use of histone deacetylase (HDAC) inhibitor is a novel therapeutic strategy for cardiovascular disease. Studies have shown that many HDAC inhibitors have the ability to reduce the aortic remodeling in various animal models. We hypothesized that the HDAC inhibitor, MGCD0103 (MGCD), attenuates aortic remodeling in rats under pressure overload-induced by transverse aortic constriction (TAC). The aortic ring tension analysis was conducted using the thoracic aorta. Sections of the aorta were visu ...[more]

PMID: 32775424

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Project description:BackgroundSevere burns, trauma and shock can cause intestinal epithelial barrier dysfunction, which can lead to intestinal endotoxemia and even sepsis and multi-organ dysfunction. Many studies have shown that histone deacetylase inhibitors (HDACIs) can improve cell tolerance to hypoxia and inflammation, thus protecting the functions of important organs in the body, and at the same time, inhibiting the degradation of tight junction (TJ) proteins, protecting the intercellular barrier, and reducing tissue edema and organ damage. However, the mechanism is unclear.MethodsEighty male Sprague-Dawley rats (weighing 280-300 g) with a 50% total body surface area full-thickness dermal burn were randomly assigned to 4 groups (20 rats/group): sham control (SC group), scald + normal saline (SN group), scald + 2-methyl-2pentenoic acid (2M2P group), and scald + valproic acid (VPA group). After scalding, we measured the following parameters at various time intervals postburn injury: intestinal mucosal injury score, diamine oxidase (DAO) activity, intestinal protein expression of acetyl histone H3 at K9 (Ac-H3K9), hypoxia inducible factor 1α (HIF-1α), erythropoietin (EPO), zonula occludens-1 (ZO-1), endothelial nitric oxide synthase (eNOS) content, nitric oxide (NO) content, and intestinal mucosal blood flow (IMBF).ResultsIntestinal mucosa showed significant morphologic injury at 4 and 8 hours after scalding that was attenuated by VPA. DAO activity in the VPA group was significantly decreased compared with the other scald groups. At 4 and 8 hours after scalding, VPA enhanced Ac-H3K9 and ZO-1 expression and decreased HIF-1α and EPO expression in the intestine compared with the other scald groups. At 4 and 8 hours after scalding, eNOS and NO protein content and IMBF in the VPA group were markedly increased compared with the other scald groups.ConclusionsHDACIs attenuated intestinal mucosal injury in fatally scalded rats. This may have involved VPA enhancing Ac-H3K9 and ZO-1 expression, inhibiting HIF-1α and EPO expression and inducing eNOS and NO increments.

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Histone Deacetylase Inhibition Attenuates Aortic Remodeling in Rats under Pressure Overload.

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Histone Deacetylase Inhibition Attenuates Aortic Remodeling in Rats under Pressure Overload.

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