Tsantan Sumtang Restored Right Ventricular Function in Chronic Hypoxia-Induced Pulmonary Hypertension Rats

Abstract

Background: Tsantan Sumtang originated from Four Tantras, which consisted of Choerospondias axillaris (Roxb.) B. L. Burtt and A. W. Hill, Santalum album L., and Myristica fragrans Houtt. The three herbs are in ratio 1:1:1. This medication is widely used for cardiovascular diseases.Aims: The purpose of this study was to explore the effect of Tsantan Sumtang on right ventricular (RV) function in hypoxia-induced pulmonary hypertension (HPH) rats and investigate the underlying mechanism.Methods: Sixty male Sprague-Dawley (SD) rats were divided into control, hypoxia, and hypoxia + Tsantan Sumtang (1.0, 1.25, and 1.5 g•kg−1•d−1) groups. Chronic hypoxia was induced by putting the rats inside a hypobaric chamber for four weeks and adjusting the inner pressure and oxygen content to match an altitude of 4500 m. Echocardiography was used to assess RV function and right ventricular-pulmonary arterial (RV-PA) coupling. The physiological parameters of the animals were also evaluated. Morphological characteristics of RV were assessed by hematoxylin and eosin (H&E) staining and TEM. Masson’s trichrome staining, immunohistochemical staining, western blotting, and TUNEL assay were used to assess fibrosis and apoptosis levels. The antioxidant and anti-apoptosis properties of Tsantan Sumtang were also evaluated. The effect of Tsantan Sumtang on ROCK signaling pathway was evaluated using real-time quantitative PCR and western blotting.Results: We established an HPH rat model as indicated by the significant increases in the physiological parameters of the rats. Tsantan Sumtang showed a significant cardiac-protective function and an improved effect on RV-PA coupling. Moreover, Tsantan Sumtang treatment inhibited fibrosis and alleviated apoptosis and oxidative stress in RV. In terms of mechanism, Tsantan Sumtang reduced the expression of ROCK (ROCK1, ROCK2) in RV, inhibited cardiac remodeling-related transcription factors (NFATc3, P-STAT3), and regulated apoptosis-related proteins.Conclusion: Tsantan Sumtang was able to restore RV function, improve RV-PA coupling, recover hemodynamic and hematological indexes, and protect RV against structural maladaptive remodeling in the HPH rats. These findings demonstrated that Tsantan Sumtang protects the function of RV in HPH rats. The antioxidant and anti-apoptosis properties of Tsantan Sumtang may be responsible for inhibiting the ROCK signaling pathway.

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

“…30 FAC (%), TAPSE/PASP, FAC/mPAP, and PASP/ESA ratios based on echocardiographic data were also found to be useful indices for evaluating RV function. 18,31 FAC and TAPSE are critical markers of RV systolic activity that are measured by echocardiography and are reliable indicators for prognosis of PAH patients. 32 As shown in Figure 2 (B) and (D), VA intervention could elevate the TAPSE index to improve the contraction and ejection of blood from the RV.…”

“…Cardiomyocyte apoptosis is a major cause of abnormal cardiac function, and it causes functional remodeling of the heart [16][17][18] The experiment was conducted based on the common apoptotic protein Bax and the apoptosis-inhibiting Bcl-2 protein. The experimental data demonstrated that the Bax protein expression level was downregulated in RV tissues of PAH rats after VA intervention, and conversely, the Bcl-2 protein expression level increased, while the Bax/Bcl-2 ratio decreased (P < .05 vs PAH group, Figure 6), indicating that VA could inhibit cardiomyocyte apoptosis in MCT-induced PAH rats.…”

Protective effect of a chronic hypobaric hypoxic environment at high altitude on cardiotoxicity induced by doxorubicin in rats: a 7 T magnetic resonance study

“…Another study recently found that compared with low-altitude residents, high-altitude patients demonstrated enhanced tolerance to inflammation and responses to I/R injury when undergoing a primary mitral valve procedure (4). To date, most experimental animal models of hypoxia have included exposure to a hypobaric chamber to simulate physiology at equivalent altitudes (30)(31)(32)(33). However, there are differences between simulated and natural highaltitude environments, such as physical activity factors and the intermittent nature of hypoxia.…”

Hypoxia-Induced Cardiomyocyte Apoptosis Exacerbates Cardiomyocyte Hypertrophy and Myocardial Injury through p38 MAPK Pathway in SD Rats

“…Studies have shown that right ventricular remodeling and its function are closely related to symptom severity and survival of HPH [6][7][8]. Increased cardiac afterload and right Disclaimer/Publisher's Note: The statements, opinions, and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s).…”