Anti-atherosclerotic activity of aqueous extract of Ipomoea batatas (L.) leaves in high-fat diet-induced atherosclerosis model rats

Objectives Cardiovascular diseases, especially atherosclerosis, are the leading cause of human mortality in Indonesia. Ipomoea batatas (L.) is a food plant used in Indonesian traditional medicine to treat cardiovascular diseases and related conditions. We assessed the anti-atherosclerotic activity of the aqueous extract of I. batatas leaves in a rat model of high-fat diet-induced atherosclerosis and its mechanism. Methods The presence of amino acid content in the I. batatas L. purple variant was determined by liquid chromatography high-resolution mass spectrometry (LC-HRMS). Thirty male Wistar rats were divided into five groups (n=6/group), i.e., standard diet group (SD), high-fat diet group (HF), and HF plus I. batatas L. extracts orally (625; 1,250; or 2,500 mg/kg) groups. The numbers of macrophages and aortic wall thickness were analyzed histologically. Immunohistochemical analyses were performed to assess foam cells-oxidized low-density lipoprotein (oxLDL), endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor (VEGF) expression in the aorta. Results LC-HRMS analysis showed nine amino acid content were identified from I. batatas L. In vivo study revealed that oral administration of I. batatas L. leaf extract alleviated foam cells-oxLDL formation and aortic wall thickness caused by high-fat diet atherosclerosis rats. Further, I. batatas L. leaf extract promoted the number of macrophages and modulated VEGF and eNOS expression in the aorta. Conclusions I. batatas L. leaf extract shows a positive anti-atherosclerosis effect. Furthermore, the mechanism may promote the macrophages, eNOS, VEGF expressions, and inhibition of foam cells-oxLDL formation and aortic wall thickness with the best dosage at 2,500 mg/kg. This could represent a novel approach to prevent cardiovascular diseases.

Multi-Omics Profiling in Marfan Syndrome: Further Insights into the Molecular Mechanisms Involved in Aortic Disease

Thoracic aortic aneurysm is a potentially life-threatening disease with a strong genetic contribution. Despite identification of multiple genes involved in aneurysm formation, little is known about the specific underlying mechanisms that drive the pathological changes in the aortic wall. The aim of our study was to unravel the molecular mechanisms underlying aneurysm formation in Marfan syndrome (MFS). We collected aortic wall samples from FBN1 variant-positive MFS patients (n = 6) and healthy donor hearts (n = 5). Messenger RNA (mRNA) expression levels were measured by RNA sequencing and compared between MFS patients and controls, and between haploinsufficient (HI) and dominant negative (DN) FBN1 variants. Immunohistochemical staining, proteomics and cellular respiration experiments were used to confirm our findings. FBN1 mRNA expression levels were highly variable in MFS patients and did not significantly differ from controls. Moreover, we did not identify a distinctive TGF-β gene expression signature in MFS patients. On the contrary, differential gene and protein expression analysis, as well as vascular smooth muscle cell respiration measurements, pointed toward inflammation and mitochondrial dysfunction. Our findings confirm that inflammatory and mitochondrial pathways play important roles in the pathophysiological processes underlying MFS-related aortic disease, providing new therapeutic options.

WRAPPING OF THE MODERATELY DILATED ASCENDING AORTA BY FRESH AUTOLOGOUS PERICARDIUM

Background and aim of the study. Wrapping of the ascending aorta (AA), isolated or associated with aortoplasty, has never been completely accepted. Some complications, as folding of the aortic wall, compression of the vasa vasorum and changes in the flow pattern, with consequent dilatation of the proximal arch, have been described. We used fresh autologous pericardium (FAP), so far never reported, to wrap the AA, with the aim to stabilize its size when moderately dilated, maintaining the preoperative dimension or limiting the reduction to a few mm. Material and Methods. From 2015 to 2019, 10 patients, who were operated on for valve or coronary surgery or both, underwent wrapping of the AA with FAP. Mean age was 69±7 years and ESII 3.5±1.7. Four patients had moderately impaired ejection fraction (35-49%). Results. There was no early or late mortality. One patient was reoperated on after 48 months for severe mitral regurgitation. At a follow up of 53±14 months, a transthoracic echocardiogram showed that the AA size reduced slightly but significantly, from 45.2±2.0 to 42.5±4.1 mm, p=0.03. The diameter of the proximal arch remained unchanged, from 37.1±1.6 to 36.3±2.9 mm, p=0.20. Conclusions. In presence of moderately dilated AA wrapping can be a reasonable option. The use of FAP stabilizes the size of the aorta after a follow up of 53 months. Maintaining a size similar to the preoperative one avoids the complications related to the procedure.

Increased Risk of Aortic Dissection with Perlecan Deficiency

Perlecan (HSPG2), a basement membrane-type heparan sulfate proteoglycan, has been implicated in the development of aortic tissue. However, its role in the development and maintenance of the aortic wall remains unknown. Perlecan-deficient mice (Hspg2−/−-Tg: Perl KO) have been found to show a high frequency (15–35%) of aortic dissection (AD). Herein, an analysis of the aortic wall of Perl KO mice revealed that perlecan deficiency caused thinner and partially torn elastic lamina. Compared to the control aortic tissue, perlecan-deficient aortic tissue showed a significant decrease in desmosine content and an increase in soluble tropoelastin levels, implying the presence of immature elastic fibers in Perl KO mice. Furthermore, the reduced expression of the smooth muscle cell contractile proteins actin and myosin in perlecan-deficient aortic tissue may explain the risk of AD. This study showed that a deficiency in perlecan, which is localized along the elastic lamina and at the interface between elastin and fibrillin-1, increased the risk of AD, largely due to the immaturity of extracellular matrix in the aortic tissue. Overall, we proposed a new model of AD that considers the deficiency of extracellular molecule perlecan as a risk factor.

Features of angioarchitectonics and structure of the aortic wall of white rats in the early stages of experimental diabetes mellitus

Background. Atherosclerotic cardiovascular diseases, as well as coronary heart disease, cerebrovascular disease, and peripheral artery disease (probably caused by atherosclerosis), are the leading cause of disability and mortality in people with diabetes. Objective. The purpose of our study was to determine the histostructural features and morphometric analysis of the components of the aortic wall and its hemomicrocirculatory bed after 2 and 4 weeks of streptozotocin-induced diabetes mellitus. Methods. The samples for the histology were the sections of the wall of the ascending part, the aortic arch, and the descending part of the aorta of 26 mature white male rats weighing 100 - 160 g. For morphometric examination, a series of images of the aortic wall was taken using a Meiji MT4300 LED microscope with an x40 objective, x10 eyepiece. Results and conclusion. The measurements were carried out using the ImageJ software. The development of micro- and macroangiopathies in experimental animals with 8-week streptozotocin-induced diabetes mellitus was histologically proved. Statistical analysis revealed a significant difference of all morphometric parameters of both - the components of the aortic wall and the vessels of its hemomicrocirculatory bed after 4 weeks of experimental diabetes in comparison with the norm, control, and the 2-nd week of the experiment. An explicit dependency of the severity of destructive changes in the wall of the aorta and links of its hemomicrocirculatory bed of vessels on the duration of the experiment was determined.

Syndecan-1 is overexpressed in human thoracic aneurysm but is dispensable for the disease progression in vivo

Glycosaminoglycans (GAGs) pooling has been considered since long as one of the histopathological characteristics defining thoracic aortic aneurysm (TAA) together with smooth muscle cells (SMCs) apoptosis and elastin fibers degradation. However, few information is provided about GAGs composition or potential implication in TAA pathology. Syndecan-1 (Sdc-1) is a heparan sulfate proteoglycan that is implicated in extracellular matrix (ECM) interaction and assembly, regulation of SMCs phenotype and various aspects of inflammation in the vascular wall. In the current work, the regulation of Sdc-1 protein was examined in human TAA by ELISA and immunohistochemistry. In addition, the role of Sdc-1 was evaluated in descending TAA in vivo using a mouse model combining both aortic wall weakening and hypertension. Our results showed that Sdc-1 protein is over expressed in human TAA aortas compared to healthy counterparts and that SMCs are the major cell type expressing Sdc-1. Similarly, in the mouse model used, Sdc-1 expression was increased in TAA aortas compared to healthy samples. Although its protective role against abdominal aneurysm has been reported, we observed that Sdc-1 was dispensable for TAA prevalence or rupture. In addition, Sdc-1 deficiency did not alter the extent of aortic wall dilatation, elastin degradation, collagen deposition, or leukocyte recruitment in our TAA model. These findings suggest that Sdc-1 could be a biomarker revealing TAA pathology. Future investigations could uncover the underlying mechanisms leading to Sdc-1 expression alteration in TAA.