Autonomic regulation of imbalance‑induced myocardial fibrosis and its mechanism in rats with cirrhosis

Abstract

The aim of the present study was to investigate the changes in cardiac function and myocardial damage in rats with cirrhosis. In addition, a secondary aim was to explore any potential changes in the expression levels of β1-adrenergic (β1) and muscarinic acetylcholine (M2) receptors . A cirrhotic cardiomyopathy (CCM) rat model was established by CCL4-oil solution for subcutaneous injection into the neck. Pathological changes in the liver and myocardial tissues were detecting by H&E staining and Masson trichrome staining. Furthermore, changes in the levels of myocardial enzymes lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB) and troponin in serum were measured by ELISA. The myocardial samples were homogenized and centrifuged. Subsequently, the supernatant was collected for detecting the expression of interleukins in myocardial tissue. Changes in the levels of inflammatory factors, IL-1, IL-2 and IL-6 both in the serum and myocardial tissue were determined by ELISA. Changes in echocardiographic measurements were evaluated using high-frequency ultrasound and the expression levels of β1 and M2 receptors in myocardial tissues were determined by western blotting. The normal lobular structure in liver tissues was found to be disappeared 8 weeks after modeling, which was replaced by pseudolobules in the rats in the CCM group. In addition, the myocardial cells were observed to be swollen and disorderly arranged. Compared with those in the control group, the left ventricular end-systolic and end-diastolic dimensions, interventricular septal dimension and LAD in rats in the CCM8 group were found to be significantly increased. The levels of myocardial enzymes LDH, CK-MB and cardiac troponin in the serum were also revealed to be significantly increased in the CCM8 group. Additionally, the levels of IL-1 and IL-6 in both serum and myocardial tissues were significantly increased in rats in the CCM8 group. However, the levels of IL-2 in both serum and myocardial tissues were decreased, which were observed alongside reductions in myocardial β1 and M2 receptor protein expression in the myocardial tissues. Taken together, these results indicate that inflammatory factors may be involved in mediating damage to the myocardium in rats with cirrhosis. During cirrhosis-induced cardiac dysfunction, there may exist a mechanism for downregulation of autonomic nerve system.

A study on the molecular mechanism of Baicalin in improving Myocardial Fibrosis based on network pharmacology and experimental verification

“…Currently, it is understood that exogenous IL-2 can enhance the response of regulatory T cells and inhibit brosis, while the function of endogenous IL-2 remains unclear [23,24]. The ndings of this study revealed an increase in protein levels of TNF-α and PTGS2 in the myocardial tissue of MF rats, accompanied by a decrease in IL-2 protein levels.…”

Pathogenic Mechanisms Underlying Cirrhotic Cardiomyopathy

“…This suggests that the positive contractile response β-adrenergic and negative contractile response to M2-receptor are attenuated in cirrhotic hearts compared with controls (Jaue et al, 1997). A recent study demonstrated that both β1 and M2 receptor protein expressions are decreased in the myocardial tissues from cirrhotic rats induced by carbon tetrachloride (Yu et al, 2021). The difference might be due to the nature of liver injury in the animal models.…”

“…The role of the microbiota in mediating cardiac disease outcomes has also been evaluated with studies finding perturbations in microbial content and metabolites potentially able to mediate cardiac dysfunction and thus overall cardiovascular disease outcomes (Beale et al, 2021). Taken together, the intra-abdominal changes associated with portal hypertension including mesenteric ischemia, alterations in gut barrier function with increase in intestinal permeability, luminal bacterial overgrowth and ultimately translocation of bacteria and or bacteria derived products that result in endotoxemia, can potentially lead to an elevation of systemic pro-inflammatory cytokines including, but not limited, to tumor necrosis factor alpha (TNFα), interleukin 1β (IL-1β) and interleukin-6 (IL-6) (Liu et al, 2000;Yu et al, 2021), that can then mediate downstream cardiac dysfunction. Currently there is a paucity of both experimental and clinical data evaluating the role of the microbiota in cirrhosis associated cardiomyopathy.…”

“…In cirrhosis, inflammatory cytokines TNFα, IL-1β (Liu et al, 2000) and IL-6 (Yu et al, 2021) are increased in cardiac tissue in cirrhotic animal models. The cardiac inflammation mediates damage to the heart which include apoptosis and hypertrophy of the cardiomyocytes, and increased rigidity of the cardiac membrane (Ma et al, 1997).…”

The Glymphatic System May Play a Vital Role in the Pathogenesis of Hepatic Encephalopathy: A Narrative Review

“…Furthermore, an autopsy study has shown ventricular hypertrophy, cardiac valve calcification, interstitial edema, fibrosis in myocytes, and coronary artery atherosclerosis in cirrhotic patients [ 65 ]. Cardiomyopathy as systolic and diastolic abnormalities, inotropic and chronotropic dysfunction, increased plasma levels of myocardial enzymes, myocyte swelling and hypertrophy, and gross abnormalities in cardiomyocytes in histological examinations have also been reported in animal models of cirrhosis and HE [ 66 , 67 , 68 , 69 ]. Reduced response to vasoconstrictors and accumulation of circulatory vasodilators, such as nitric oxide, carbon monoxide, and endocannabinoids explain the suppression of systemic vascular resistance in liver failure [ 70 , 71 , 72 , 73 ].…”