Cardiac Lymphatics and Therapeutic Prospects in Cardiovascular Disease: New Perspectives and Hopes.

The lymphatic system is the same reticular fluid system as the circulatory system found throughout the body in vascularized tissues. Lymphatic vessels are low-pressure, blind-ended tubular structures that play a crucial role in maintaining tissue fluid homeostasis, immune cell transport, and lipid absorption. The heart also has an extensive lymphatic network, and as research on cardiac lymphatics has progressed in recent years, more and more studies have found that cardiac lymphangiogenesis may ameliorate certain cardiovascular diseases, and therefore stimulation of cardiac lymphangiogenesis may be an important tool in the future treatment of cardiovascular diseases. This article briefly reviews the development and function of cardiac lymphatic vessels, the interaction of cardiac lymphatic vessels with cardiovascular diseases (including atrial fibrillation, coronary atherosclerosis, and heart failure), and finally discusses the therapeutic potential of targeted cardiac lymphatic therapy for cardiovascular diseases.

Association between interatrial septum adiposity and atrial fibrillation: transesophageal echocardiography imaging and autopsy study.

Recent clinical evidence has suggested that interatrial septal (IAS) adiposity contributes to atrial fibrillation (AF). The present study aimed to confirm the usefulness of transesophageal echocardiography (TEE) to estimate IAS adiposity in patients with AF. The histological IAS analysis based on autopsy samples sought to clarify characteristics that underlie the contribution of IAS adiposity to AF. The imaging study analyzed the TEE results in patients with AF (n = 184) in comparison with transthoracic echocardiography (TTE) and computed tomography (CT) results. The autopsy study histologically analyzed IAS in subjects with (n = 5) and without (n = 5) history of AF. In the imaging study, the ratio of interatrial septum adipose tissue (IAS-AT) volume per epicardial adipose tissue (EpAT) volume was greater in patients with persistent AF compared (PerAF) to those with paroxysmal AF (PAF). Multivariable analysis revealed that both TEE-assessed IAS thickness and TTE-assessed left atrial dimension were predicted by CT-assessed IAS-AT volume. In the autopsy study, the histologically-assessed IAS section thickness was greater in the AF group than that in the non-AF group and was positively correlated with the IAS-AT area percentage. In addition, the size of adipocytes in IAS-AT was smaller, compared to EpAT and subcutaneous adipose tissue (SAT). IAS-AT infiltrated into the IAS myocardium, as if adipose tissue split the myocardium (designated as myocardial splitting by IAS-AT). The number of island-like myocardium pieces as a result of myocardial splitting by IAS-AT was greater in the AF group than in the non-AF group and was positively correlated with the IAS-AT area percentage. The present imaging study confirmed the usefulness of TEE to estimate IAS adiposity in patients with AF without radiation exposure. The autopsy study suggested that the myocardial splitting by IAS-AT may contribute to atrial cardiomyopathy leading to AF.

The Predictive Value of Epicardial Fat Tissue Volume in the Occurrence and Development of Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Background: Atrial fibrillation (AF) is one of the most common arrhythmias in clinical practice. Although fat is currently considered to be a risk factor for AF and a pathogenic link between epicardial fat tissue (EFT) and AF has been speculated, there are currently few clinical studies and literature data domestically or abroad. Objective: This study conducted a meta-analysis of observational case series studies to verify the relationship between atrial fibrillation and EFT and to strengthen the predictive value of EFT in the occurrence, development, and postablative recurrence of AF. Methods: We conducted a systematic search of the literature in electronic databases until December 2021 and supplemented this through manual searches of individual studies, reviewed articles, and reference lists in conference proceedings. This study conducted a meta-analysis to compare the differences between different populations, such as healthy participants and AF patients, healthy subjects and AF subtype cases, and paroxysmal and persistent AF with AF recurrence and without AF recurrence after ablation. Results: Following the retrieval of 828 articles, only 22 articles were selected as research results. Accordingly, the meta-analysis results show that the volume of EFT in AF is greater than that in healthy subjects (MD = 39.34 ml, 95% CI = 27.11, 51.58); persistent AF is greater than paroxysmal AF (MD = 14.37 ml, 95% CI = 7.46, 21.27); and recurrence after ablation is greater than without recurrence (MD = 14.37 ml, 95% CI = 7.46, 21.27). Conclusion: The results of this study further confirm the connection between EFT and AF and that EFT has a certain predictive value for the occurrence and development of AF.

Pharmacological activation of estrogenic receptor G protein-coupled receptor 30 attenuates angiotensin II-induced atrial fibrosis in ovariectomized mice by modulating TGF-ß1/smad pathway.

BACKGROUND: G-protein-coupled ER (GPR30) plays an important role in cardioprotection. Recent studies have shown that the GPR30-specific agonist G-1 reduces the degree of myocardial fibrosis in rats with myocardial infarction, reduces the morbidity associated with atrial fibrillation, and inhibits the proliferation of cardiac fibroblasts in animal experiments. Nevertheless, the underlying mechanism of myocardial fibrosis and atrial fibrillation remains unclear. In this study, we explored the mechanism underlying the effect of GPR30 on atrial fibrosis and atrial fibrillation in OVX mice. METHODS: We established an animal model of atrial fibrillation induced by Ang II (derived from OVX C57BL/6 female mice) and observed the role of G-1 in cardiac function by echocardiography, hemodynamics, morphology and fibrosis-related and apoptosis-related protein expression by Masson's trichrome, immunofluorescence, western blotting and TUNEL staining. RESULTS: Echocardiography and body surface ECG showed that G-1 combined with Ang II significantly reduced atrial fibrosis and atrial fibrillation compared to Ang II alone. The G-1 treatment group exhibited changes in the mRNA and protein expression of apoptosis-related genes. Moreover, G-1 treatment also altered the levels of inflammation-related proteins and mRNAs. In primary cultured cardiac fibroblasts (CFSs), proliferation was significantly increased in response to Ang II, and G-1 inhibited cell proliferation and apoptosis. CONCLUSION: GPR30 is a potential therapeutic target for alleviating atrial fibrosis in OVX mice by upregulating Smad7 expression to inhibit the TGF-ß/Smad pathway.

A traditional herbal medicine rikkunshito prevents angiotensin II-Induced atrial fibrosis and fibrillation.

BACKGROUND: Rikkunshito (RKT), a traditional herbal medicine, has been demonstrated to exert anti-inflammatory, anti-apoptotic, and anti-fibrotic effects in several organs. This study tested the hypothesis that RKT can suppress angiotensin II (AngII)-induced inflammatory atrial fibrosis and ameliorate enhanced vulnerability to atrial fibrillation (AF). METHODS: Eight-week-old male C57BL/6 mice were subcutaneously infused with either vehicle or AngII (2.0 mg/kg/day) for 2 weeks. Water or RKT at a dose of 1000 mg/kg/day were orally administered once daily for 2 weeks. Morphological, histological, and biochemical analyses were performed. AF was induced either by transesophageal burst pacing in vivo or by burst/extrastimuli in isolated perfused hearts using a Langendorff apparatus. RESULTS: RKT at a dose of 1000 mg/kg/day for 2 weeks attenuated atrial interstitial fibrosis and profibrotic and proinflammatory signals induced by continuous infusion of AngII. RKT attenuated AngII-induced enhanced vulnerability to AF in in vivo experiments and in isolated perfused hearts. Atractylodin, an active component of RKT, exhibited antifibrotic activity comparable to that of RKT. RKT reversed AngII-induced suppression of sirtuin 1 (Sirt1) translocation to the nuclei. RKT suppressed AngII-induced phosphorylation of IκB, overexpression of p53, and cellular apoptotic signals and apoptosis. All of the antagonizing effects of RKT against AngII were attenuated by a concomitant treatment with a growth hormone secretagogue receptor (GHSR)-inhibitor. CONCLUSION: Our results demonstrated that RKT prevented atrial fibrosis and attenuated enhanced vulnerability to AF induced by AngII. The results also suggested that potentiating the GHSR-Sirt1 pathway is involved in these processes.