Hypothalamic miR-204 Induces Alteration of Heart Electrophysiology and Neurogenic Hypertension by Regulating the Sympathetic Nerve Activity: Potential Role of Microbiota

Abstract

There is abundant evidence demonstrating the association between gut dysbiosis and neurogenic diseases such as hypertension. A common characteristic of resistant hypertension is the chronic elevation in sympathetic nervous system (SNS) activity accompanied by increased release of norepinephrine (NE), indicating a neurogenic component that contributes to the development of hypertension. Factors that modulate the sympathetic tone to the cardiovascular system in hypertensive patients are still poorly understood. Research has identified an interaction between the brain and the gut, and this interaction plays a possible role in the mechanism of heart damage-induced hypertension. Data, however, remain scarce, and further study is required to define the role of microbiota in sympathetic neural function and its relationship with heart damage and blood pressure (BP) control. Experimental evidence has pointed toward a bidirectional relationship between alterations in the types of bacteria present in the gut and neurogenic diseases, such as hypertension. Our published data showed that miR-204, a microRNA that plays an important role in the CNS function, is affected by gut dysbiosis. Therefore, miR-204 could be a key element that regulates normal sinus rhythm and neuronal hypertension. In this review, we will shed light on the potential mechanism by which microbiota affects hypothalamic miR-204, which in turn, could hinder the sympathetic nerve drive to the cardiovascular system leading to arrhythmia and hypertension.

Non-Coding RNAs and Gut Microbiota in the Pathogenesis of Cardiac Arrhythmias: The Latest Update

“…Through a variety of pathways, the gut microbiota could significantly regulate the development of cardiac arrhythmias, which may provide an extensive range of possible therapeutic approaches [ 58 , 59 ]. For example, experimental evidence has indicated a bidirectional relationship between alterations in the categories of bacteria present in the gut and neurogenic diseases, including hypertension, which might also function as a molecular dispatch that could convert gut bacterial signals into a neural yield that could also influence hypertension and/or cardiac electrophysiology [ 58 ]. In addition, it has been suggested that the role of the gut microbiota and its metabolites might be involved in the pathogenesis as well as the prognostic value of many cardiovascular diseases [ 59 ].…”

“…As mentioned before, miR-122-5p could possess great diagnostic potential in arrhythmogenic cardiomyopathy patients [40,57] (Figure 2). yield that could also influence hypertension and/or cardiac electrophysiology [58]. In a dition, it has been suggested that the role of the gut microbiota and its metabolites mig be involved in the pathogenesis as well as the prognostic value of many cardiovascul diseases [59].…”

“…Tob1 may be inactivate In these ways, data from several studies in both experimental animals and clinical humans may suggest that the role of the gut microbiota and its metabolites in arrhythmogenicity is well interconnected. Through a variety of pathways, the gut microbiota could significantly regulate the development of cardiac arrhythmias, which may provide an extensive range of possible therapeutic approaches [58,59]. For example, experimental evidence has indicated a bidirectional relationship between alterations in the categories of bacteria present in the gut and neurogenic diseases, including hypertension, which might also function as a molecular dispatch that could convert gut bacterial signals into a neural yield that could also influence hypertension and/or cardiac electrophysiology [58].…”

MicroRNAs in Inflammatory Bowel Disease and Its Complications

“…Impaired vasorelaxation is a marker for early atherosclerosis, and it is proposed that phosphorylated STAT3, a repressor of miR-204, is a potential gut–heart signaling target as it was subsequently downregulated in mice with high-fat diets, though it is potentially not the only target, as Sirt1 knockout did not completely ameliorate miR-204 upregulation. Gut dysbiosis may also impact hypothalamic miR-204, as studies show an association between decreased hypothalamic miR-204 and increased hypothalamic brain-derived naturopathic factor (BDNF) [ 64 ]. Increased BDNF in the hypothalamic paraventricular nucleus is associated with arrhythmia, hypertension, and sympathetic activity, which indicates that gut dysbiosis may alter cardiovascular activity through indirect neurogenic pathways.…”

“…The gut and brain also display remotely mediated crosstalk, as Jang et al showed that fecal microbiota transplant (FMT) from patients with IBD with or without depression significantly increased anxiety-like behaviors within mice, and mice transplanted with FMTs from patients with IBD and depression showed depression-like behaviors as well [ 71 ]. There is also evidence that IBD can facilitate organizational changes within neurological structures, which could be mediated by miRNAs [ 64 ].…”