Dataset Information

Punicalagin attenuates ventricular remodeling after acute myocardial infarction via regulating the NLRP3/caspase-1 pathway.

ABSTRACT:

Context

Punicalagin has myocardial protection; the mechanism of punicalagin on ventricular remodeling (VR) after acute myocardial infarction (AMI) remains unclear.

Objective

These studies explore the role and mechanism of punicalagin in preventing and treating VR after AMI.

Materials and methods

Molecular docking was used to predict the targets of punicalagin. After 2 weeks of AMI model, the SD rats were randomly divided into model, and punicalagin (200, 400 mg/kg, gavage) groups for 4 weeks. Thoracotomy with perforation but no ligature was performed on rats in control group. The protein expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis speck-like protein (ASC), caspase-1, gasdermin D (GSDMD), and GSDMD-N, the mRNA expression of NLRP3, caspase-1, GSDMD, interleukin-1β (IL-1β) and IL-18 were evaluated.

Results

Punicalagin had binding activities with NLRP3 (Vina score, -5.8), caspase-1 (Vina score, -6.7), and GSDMD (Vina score, -6.7). Punicalagin could improve cardiac function, alleviate cardiac pathological changes, minimize the excessive accumulation of collagen in the left ventricular myocardium (p < 0.01), and inhibit cardiomyocyte apoptosis (p < 0.01). Furthermore, punicalagin could inhibit the overexpression of NLRP3, caspase-1, and GSDMD via immunohistochemistry (p < 0.01). Punicalagin inhibited the protein levels of NLRP3, caspase-1, ASC, GSDMD, and GSDMD-N (p < 0.05, p < 0.01). Punicalagin reduced the mRNA expression of NLRP3, caspase-1, GSDMD, IL-1β and IL-18 (p < 0.05, p < 0.01).

Conclusions

Punicalagin may provide a useful treatment for the future myocardial protection.

SUBMITTER: Peng JF

PROVIDER: S-EPMC10294732 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Punicalagin attenuates ventricular remodeling after acute myocardial infarction via regulating the NLRP3/caspase-1 pathway.

Peng Jian-Fei JF Zhao Xiao-Ni XN Zhang Meng M Li Jing-Ya JY Zhao Chun-Chun CC Wang Shu-Shu SS Wang Jia-Li JL Shi Hui H Zhou Peng P Wang Liang L

Pharmaceutical biology 20231201 1

<h4>Context</h4>Punicalagin has myocardial protection; the mechanism of punicalagin on ventricular remodeling (VR) after acute myocardial infarction (AMI) remains unclear.<h4>Objective</h4>These studies explore the role and mechanism of punicalagin in preventing and treating VR after AMI.<h4>Materials and methods</h4>Molecular docking was used to predict the targets of punicalagin. After 2 weeks of AMI model, the SD rats were randomly divided into model, and punicalagin (200, 400 mg/kg, gavage) ...[more]

PMID: 37357417

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Project description:PurposeNitric oxide (NO) is constitutively produced and released from the endothelium and several blood cell types by the isoform 3 of the NO synthase (NOS3). We have shown that NO protects against myocardial ischemia/reperfusion (I/R) injury and that depletion of circulating NOS3 increases within 24 h of ischemia/reperfusion the size of myocardial infarction (MI) in chimeric mice devoid of circulating NOS3. In the current study we hypothesized that circulating NOS3 also affects remodeling of the left ventricle following reperfused MI.MethodsTo analyze the role of circulating NOS3 we transplanted bone marrow of NOS3-/- and wild type (WT) mice into WT mice, producing chimerae expressing NOS3 only in vascular endothelium (BC-/EC+) or in both, blood cells and vascular endothelium (BC+/EC+). Both groups underwent 60 min of coronary occlusion in a closed-chest model of reperfused MI. During the 3 weeks post MI, structural and functional LV remodeling was serially assessed (24 h, 4 d, 1 w, 2 w and 3 w) by echocardiography. At 72 hours post MI, gene expression of several extracellular matrix (ECM) modifying molecules was determined by quantitative RT-PCR analysis. At 3 weeks post MI, hemodynamics were obtained by pressure catheter, scar size and collagen content were quantified post mortem by Gomori's One-step trichrome staining.ResultsThree weeks post MI, LV end-systolic (53.2±5.9 μl; ***p≤0.001; n = 5) and end-diastolic volumes (82.7±5.6 μl; *p<0.05; n = 5) were significantly increased in BC-/EC+, along with decreased LV developed pressure (67.5±1.8 mm Hg; n = 18; ***p≤0.001) and increased scar size/left ventricle (19.5±1.5%; n = 13; **p≤0.01) compared to BC+/EC+ (ESV: 35.6±2.2 μl; EDV: 69.1±2.6 μl n = 8; LVDP: 83.2±3.2 mm Hg; n = 24; scar size/LV13.8±0.7%; n = 16). Myocardial scar of BC-/EC+ was characterized by increased total collagen content (20.2±0.8%; n = 13; ***p≤0.001) compared to BC+/EC+ (15.9±0.5; n = 16), and increased collagen type I and III subtypes.ConclusionCirculating NOS3 ameliorates maladaptive left ventricular remodeling following reperfused myocardial infarction.

Dataset Information

Punicalagin attenuates ventricular remodeling after acute myocardial infarction via regulating the NLRP3/caspase-1 pathway.

Context

Objective

Materials and methods

Results

Conclusions

Publications

Punicalagin attenuates ventricular remodeling after acute myocardial infarction via regulating the NLRP3/caspase-1 pathway.

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