Vanillic Acid Alleviates Right Ventricular Function in Rats With MCT-Induced Pulmonary Arterial Hypertension

Abstract

This study examined the molecular processes behind the effects of vanillic acid (VA) on right ventricular (RV) hypertrophy and function in rats with monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). There were 40 male Sprague‒Dawley (SD) rats that were separated into 4 groups: Control, PAH, MCT + VA (50 mg/kg/d), and MCT + VA (100 mg/kg/d). Male SD rats were injected with MCT once under the skin to create the PAH model (40 mg/kg). RV morphological properties were evaluated using Masson and hematoxylin and eosin (H&E) staining. Echocardiography was used to evaluate RV functioning and right ventricle–pulmonary artery (RV-PA) coupling. In addition, Rho-associated protein kinase (ROCK) pathway-related factors were evaluated using Western blotting. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory markers as well as atrial natriuretic peptide (ANP) and brain-type natriuretic peptide (BNP) in the blood of PAH rats. As a result, VA effectively reduced the development of RV cardiomyocyte hypertrophy and fibrosis in PAH rats; levels of ANP, BNP, and inflammatory markers in the blood of PAH rats were also significantly decreased by VA intervention. Additionally, VA enhanced RV functioning and RV-PA coupling in PAH rats. In response to VA, the expression of proteins related to the ROCK pathway (ROCK1, ROCK2, NFATc3, P-STAT3, and Bax) was downregulated, whereas Bcl-2 expression was elevated. This study found that VA could attenuate RV remodeling and improve RV-PA coupling in PAH rats. RV remodeling and dysfunction may be linked to the dysregulation of the ROCK pathway, and the protective action of VA on RV function may be due to a block in the ROCK signaling pathway or its downstream signaling molecules.

In vivo pharmacokinetic study of vanillic acid in monocrotaline‐induced pulmonary arterial hypertension rats and its tissue distribution

“…A previous study found that VA could alleviate pulmonary vascular remodeling by enhancing NO signaling pathways in MCT‐induced PAH rat (Wang et al, 2022). We also found that VA had a significant intervention effect on right ventricular remodeling and right ventricular function in MCT‐induced PAH rat (J. Chen et al, 2023). However, its efficacy was not shown to be dose dependent and we wondered whether the bioavailability of VA in PAH rats had changed.…”

“…We also found that VA had a significant intervention effect on right ventricular remodeling and right ventricular function in MCT-induced PAH rat (J. Chen et al, 2023). However, its efficacy was not shown to be dose dependent and we wondered whether the bioavailability of VA in PAH rats had changed.…”

Bioactive Compounds and Cardiac Fibrosis: Current Insight and Future Prospect

“…Further research is necessary to fully understand the mechanisms by which probiotics influence cardiac fibrosis and their overall effects on the gut microbiome in the context of different disease conditions. Piperine Alkaloids nigrum) [171,202] Ginsenoside Saponins Ginseng root [173] Astragaloside IV Saponins Astragalus membranaceus [172] Coumarins Coumarins tonka bean, cassia bark [174] Stilbenes Stilbenes grapes, peanuts, and berries [150,177] Caffeic acid Phenolic acids apples and red wine [178,179] Chlorogenic acid Phenolic acids Coffee [180,181] Vanillic acid Phenolic acids vanilla beans [182] Anthocyanins Anthocyanins red and purple berries, grapes, apples, plums, cabbage, or foods containing high levels of natural colorants [183] Tannins Tannins plant-based foods and beverages, such as tea, coffee, and wine [184] tonka bean, cassia bark [174] Stilbenes Stilbenes…”

“…Astragaloside IV Saponins Astragalus membranaceus [172] Coumarins Coumarins tonka bean, cassia bark [174] Stilbenes Stilbenes grapes, peanuts, and berries [150,177] Caffeic acid Phenolic acids apples and red wine [178,179] Chlorogenic acid Phenolic acids Coffee [180,181] Vanillic acid Phenolic acids vanilla beans [182] Anthocyanins Anthocyanins red and purple berries, grapes, apples, plums, cabbage, or foods containing high levels of natural colorants [183] Tannins Tannins plant-based foods and beverages, such as tea, coffee, and wine [184] red and purple berries, grapes, apples, plums, cabbage, or foods containing high levels of natural colorants [183] Tannins Tannins…”

“…Vanillic acid, which is a phenolic compound widely found in plants and fruits, has a protective role on right-ventricular function by inhibiting the Rho-associated protein kinase signaling pathway. It may also prevent cardiac fibrosis, promote cardiomyocyte enlargement, and prevent cardiomyocyte apoptosis in Rats with Monocrotaline-Induced Pulmonary Arterial Hypertension [182]. While these studies suggest that phenolic acids may have potential benefits for cardiac fibrosis, more research is needed to confirm these effects in humans.…”