Cannabidiol alleviates right ventricular fibrosis by inhibiting the transforming growth factor β pathway in monocrotaline-induced pulmonary hypertension in rats

Krzyżewska, Anna; Baranowska-Kuczko, Marta; Kasacka, Irena; Kozłowska, Hanna

doi:10.1016/j.bbadis.2023.166753

Cited by 6 publications

(9 citation statements)

References 48 publications

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“…We showed neither beneficial nor adverse effects of CBD administration on plasma parameters. Still, we observed prevention of liver enlargement in the MCT + CBD group compared to MCT rats, presumably through the beneficial effect on RV function that we have already demonstrated in our previous studies [ 9 , 10 ]. Thus, we confirmed the results of other authors where chronic (90 days) oral administration of CBD at doses of 0.66 and 1.33 mg/kg to healthy rats did not modify the most biochemical parameters (e.g., AST, ALT) and did not modify liver weight or liver/body weight ratio [ 26 ].…”

Section: Discussionsupporting

confidence: 65%

“…It may indicate the onset of CH development in the MCT group due to passive blood stasis in the liver caused by RV failure rather than toxic MCT-induced liver damage. Our previous papers support these speculations as using the same rats, we have demonstrated PH with RV failure as evidenced by increased RVSP, elevated Fulton index (the RV weight to the left ventricle (LV) plus septum (RV/LV + S) ratio) [ 9 ], as well as cardiomyocyte enlargement and RV fibrosis [ 10 ]. Dai et al [ 3 ] also did not show an increase in ALT, AST, GGT, and total bilirubin in the serum of patients with CH.…”

Section: Discussionmentioning

confidence: 53%

“…It has been demonstrated that CBD, alleviates MCT-induced PH in rats [ 9 , 12 ] and Sugen + hypoxia-induced PH in mice by reducing RV systolic pressure (RVSP) [ 12 ]. In previous publications, we also proved that CBD reduces pulmonary and RV hypertrophy, reduces perivascular and interstitial fibrosis in the RV as well as lowers plasma pro-B-type natriuretic peptide (NT-proBNP) levels in MCT-induced PH [ 9 , 10 ]. Moreover, CBD reduced fibrosis in the left ventricle in a mouse model of autoimmune myocarditis [ 13 ].…”

Section: Introductionmentioning

confidence: 83%

“…The pathophysiology of cardiac-hepatic interactions is not fully understood and it is a subject of intense scientific interest, requiring a well-defined animal model [ 8 ]. The animal model of monocrotaline (MCT)-induced PH is one of the most widely used animal models that allow for the development of severe PH, RV hypertrophy, and subsequent CH [ 6 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Cannabidiol may prevent the development of congestive hepatopathy secondary to right ventricular hypertrophy associated with pulmonary hypertension in rats

Krzyżewska,

Baranowska-Kuczko,

Galicka

et al. 2024

Pharmacol. Rep

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Background Pulmonary hypertension (PH) can cause right ventricular (RV) failure and subsequent cardiohepatic syndrome referred to as congestive hepatopathy (CH). Passive blood stasis in the liver can affect inflammation, fibrosis, and ultimately cirrhosis. Cannabidiol (CBD) has many beneficial properties including anti-inflammatory and reduces RV systolic pressure and RV hypertrophy in monocrotaline (MCT)-induced PH in rats. Thus, it suggests that CBD may have the potential to limit CH development secondary to RV failure. The present study aimed to determine whether chronic administration of CBD can inhibit the CH secondary to RV hypertrophy associated with MCT-induced PH. Methods The experiments involved rats with and without MCT-induced PH. CBD (10 mg/kg) or its vehicle was administered once daily for 3 weeks after MCT injection (60 mg/kg). Results Monocrotaline administration increased the liver/body weight ratio. In histology examinations, we observed necrosis and vacuolar degeneration of hepatocytes as well as sinusoidal congestion. In biochemical studies, we observed increased levels of nuclear factor-κappa B (NF-κB), tumour necrosis factor-alpha (TNA-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). CBD administration to PH rats reduced the liver/body weight ratio, improved the architecture of the liver, and inhibited the formation of necrosis. Cannabidiol also decreased the level of NF-κB, TNF-α, IL-1β and IL-6. Conclusions The studies show that CBD can protect the liver from CH probably through attenuating PH, protective effects on the RV, and possibly direct anti-inflammatory effects on liver tissue through regulation of the NF-κB pathway. Graphical abstract

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

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Cannabidiol may prevent the development of congestive hepatopathy secondary to right ventricular hypertrophy associated with pulmonary hypertension in rats

Krzyżewska,

Baranowska-Kuczko,

Galicka

et al. 2024

Pharmacol. Rep

Self Cite

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“…TGF‐β, as the principal cytokine governing ECM metabolism, exerts an impact on the expression of elastin, collagen, and fibronectin 52 . TGF‐β signaling has been linked to both nonhereditary and specific hereditary cardiovascular ailments, 53 including atherosclerosis, 54 and cardiac fibrosis 55 . As early as 2004, 56 research has demonstrated that the inhibitory effect of SMAD7‐Smurf‐mediated TGF‐β signaling could significantly contribute to maintaining the autocrine TGF‐β loop in fibrotic disorders, thereby mitigating tissue damage.…”

Section: Cardiovascular Diseasesmentioning

confidence: 99%

The role of SMURFs in non‐cancerous diseases

et al. 2023

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The ubiquitin‐proteasome system is a crucial mechanism for regulating protein levels in cells, with substrate‐specific E3 ubiquitin ligases serving as an integral component of this system. Among these ligases are SMAD‐specific E3 ubiquitin‐protein ligase 1 (SMURF1) and SMAD‐specific E3 ubiquitin‐protein ligase 2 (SMURF2), which belong to the neural precursor cell‐expressed developmentally downregulated 4 (NEDD4) subfamily of Homologous to E6‐AP COOH terminus (HECT)‐type E3 ligases. As E3 ligases, SMURFs have critical functions in regulating the stability of multiple proteins, thereby maintaining physiological processes such as cell migration, proliferation, and apoptosis. The occurrence of many diseases is attributed to abnormal cell physiology and an imbalance in cell homeostasis. It is noteworthy that SMURFs play pivotal roles in disease progression, with the regulatory functions being complex and either facilitative or inhibitory. In this review, we elucidate the mechanisms by which SMURF1 and SMURF2 can regulate disease progression in non‐cancerous diseases. These significant findings offer potential novel therapeutic targets for various diseases and new avenues for research on SMURF proteins.

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Immunomodulatory macrophages and Treg in pulmonary hypertension

Olajuyin,

Zhang

et al. 2023

Comp Clin Pathol

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Cannabidiol alleviates right ventricular fibrosis by inhibiting the transforming growth factor β pathway in monocrotaline-induced pulmonary hypertension in rats

Cited by 6 publications

References 48 publications

Cannabidiol may prevent the development of congestive hepatopathy secondary to right ventricular hypertrophy associated with pulmonary hypertension in rats

Cannabidiol may prevent the development of congestive hepatopathy secondary to right ventricular hypertrophy associated with pulmonary hypertension in rats

The role of SMURFs in non‐cancerous diseases

Immunomodulatory macrophages and Treg in pulmonary hypertension

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