Apolipoprotein A1-Related Proteins and Reverse Cholesterol Transport in Antiatherosclerosis Therapy: Recent Progress and Future Perspectives

Hyperlipidemia characterized by abnormal deposition of cholesterol in arteries can cause atherosclerosis and coronary artery occlusion, leading to atherosclerotic coronary heart disease. The body prevents atherosclerosis by reverse cholesterol transport to mobilize and excrete cholesterol and other lipids. Apolipoprotein A1, the major component of high-density lipoprotein, plays a key role in reverse cholesterol transport. Here, we reviewed the role of apolipoprotein A1-targeting molecules in antiatherosclerosis therapy, in particular ATP-binding cassette transporter A1, lecithin-cholesterol acyltransferase, and scavenger receptor class B type 1.

Impact of the Main Cardiovascular Risk Factors on Plasma Extracellular Vesicles and Their Influence on the Heart’s Vulnerability to Ischemia-Reperfusion Injury

The majority of cardiovascular deaths are associated with acute coronary syndrome, especially ST-elevation myocardial infarction. Therapeutic reperfusion alone can contribute up to 40 percent of total infarct size following coronary artery occlusion, which is called ischemia-reperfusion injury (IRI). Its size depends on many factors, including the main risk factors of cardiovascular mortality, such as age, sex, systolic blood pressure, smoking, and total cholesterol level as well as obesity, diabetes, and physical effort. Extracellular vesicles (EVs) are membrane-coated particles released by every type of cell, which can carry content that affects the functioning of other tissues. Their role is essential in the communication between healthy and dysfunctional cells. In this article, data on the variability of the content of EVs in patients with the most prevalent cardiovascular risk factors is presented, and their influence on IRI is discussed.

Vena cava presents endothelial dysfunction prior to thoracic aorta in heart failure: the pivotal role of nNOS uncoupling/ oxidative stress

Arterial endothelial dysfunction has been extensively studied in heart failure (HF). However little is known about the adjustments shown by the venous system in this condition. Considering that inferior vena cava (VC) tone could influence cardiac performance and HF prognosis, the aim of the present study was to assess the VC and thoracic aorta (TA) endothelial function of HF-post-myocardial infarction (MI) rats, comparing both endothelial responses and signaling pathways developed. Vascular reactivity of TA and VC from HF post-MI and sham operated (SO) rats was assessed with a wire myograph, four weeks after coronary artery occlusion surgery. Nitric oxide (NO), H2O2 production and oxidative stress were evaluated in situ with fluorescent probes, whilst protein expression and dimer/monomer ratio was assessed by western blot. VC from HF rats presented endothelial dysfunction, while TA exhibited higher acetylcholine (ACh)-induced vasodilation when compared to vessels from SO rats. TA exhibited increased ACh-induced NO production due to a higher coupling of endothelial and neuronal NO synthases isoforms (eNOS, nNOS), and enhanced expression of antioxidant enzymes. These adjustments, however, were absent in VC of HF post-MI rats, which exhibited uncoupled nNOS, oxidative stress and higher H2O2 bioavailability. Altogether, this study suggests a differential regulation of endothelial function between VC and TA of HF post-MI rats, most likely due to nNOS uncoupling and compromised antioxidant defense.

Impact of Ghrelin on Ventricular Arrhythmia and Related Mechanism After Myocardial Infarction

<b><i>Introduction:</i></b> Ghrelin is an endogenous peptide with potential protective effects on ischemic heart. <b><i>Methods:</i></b> Synthetic ghrelin was administered (100 μg·kg^-1 subcutaneous injection, twice daily) for 4 weeks in a rat model of myocardial infarction (MI) with coronary artery occlusion. At the 5th week, electrocardiogram, monophasic action potentials and autonomic nerve function were evaluated. Cardiac tyrosine hydroxylase (TH) was determined by immunofluorescence staining. <b><i>Results:</i></b> MI significantly increased sympathetic nerve activity (SNA) and ventricular arrhythmias, and prolonged APD dispersion and APD alternans (<i>p</i> &#x3c; 0.01). Ghrelin treatment significantly increased ventricular fibrillation threshold (VFT), shortened APD dispersion and APD alternans, inhibited SNA and promoted vagus nerve activities (<i>p</i> &#x3c; 0.01). Ghrelin also markedly reversed abnormal expression of TH in the peri-infarcted area of the heart (<i>p</i> &#x3c; 0.01). <b><i>Discussion/Conclusion:</i></b> Ghrelin provides a sustained electrophysiological protection by the increase of VFT and improvement of APD dispersion and APD alternans. The mechanism may be related to the regulation of autonomic nerve and sympathetic nerve remodeling. Thus, ghrelin represents a novel drug to prevent ventricular arrhythmia in ischemic heart disease.

Basilica procedure for prevention of coronary obstruction during transcatheter aortic valve implantation: case report from Latam

Transcatheter aortic valve implantation is considered a standard treatment for many symptomatic patients with severe aortic stenosis. Coronary artery occlusion after transcatheter aortic valve implantation is associated with a mortality rate of up to 50%. In this case report we described a patient with severe aortic bioprosthesis dysfunction, at high risk of coronary obstruction after transcatheter aortic valve implantation. This patient underwent Basilica procedure followed by valve-in-valve transcatheter aortic valve implantation. The patient demonstrated good improvement and was discharged from hospital after 2 days, without any symptoms. The patient remained asymptomatic at 6 months of follow-up.

Epicardial transplantation of autologous atrial appendage micrografts–evaluation of safety and feasibility in pigs after coronary artery occlusion

Several approaches devised for clinical utilization of cell-based therapies for heart failure often suffer from complex and lengthy preparation stages. Epicardial delivery of autologous atrial appendage micrografts (AAMs) with a clinically used extracellular matrix (ECM) patch provides a straightforward therapy alternative. We evaluated the operative feasibility and the effect of micrografts on the patch-induced epicardial foreign body inflammatory response in a porcine model of myocardial infarction. Right atrial appendages were harvested and mechanically processed into AAMs. The left anterior descending coronary artery was ligated to generate acute infarction. Patches of ECM matrix with or without AAMs were transplanted epicardially onto the infarcted area. Four pigs received the ECM and four received the AAMs patch. Cardiac function was studied by echocardiography both preoperatively and at three weeks follow-up. The primary outcome measures were safety and feasibility of the therapy administration and the secondary outcome was the inflammatory response to ECM. Neither AAMs nor ECM patch-related complications were detected during the follow-up time. AAMs patch preparation was feasible according to time and safety. Inflammation was greatly reduced in AAMs as compared to ECM patches as measured by the amount of infiltrated inflammatory cells and area of inflammation. Immunohistochemistry demonstrated an increased CD3+ cell density in the AAMs patch infiltrate. Epicardial AAMs transplantation demonstrated safety and clinical feasibility. The use of micrografts significantly inhibited ECM-induced foreign body inflammatory reactivity. Transplantation of AAMs shows good clinical applicability as adjuvant therapy to cardiac surgery and can suppress acute inflammatory reactivity.