Brucellosis relapse causing thoracic aortic ulcers and aneurysm formation: a case report

Background Brucellosis is an infectious disease caused by Brucella spp, which can involve the cardiovascular, digestive, and respiratory systems. Cardiovascular involvement is a rare occurrence, it has an extremely high mortality rate. Case presentation A 67-year-old Chinese man presented with thoracic aortic multiple ulcers and partial aneurysm formation that caused symptoms of left waist and left buttock pain. The man was admitted to our hospital due to abdominal aorta pseudoaneurysms 5 years ago. The diagnosis was made by thoracic computed tomography angiography (CTA), previous history, and positive culture of Brucella, and the patient was successfully treated by thoracic aortic covered stent-graft implantation and specific medical treatment. Conclusions People who have a history of contact with cattle and sheep, should beware of the possibility of Brucella infection. If chest and abdominal pain occur, timely medical treatment is recommended, aortic aneurysm, the disease with a high risk of death, can be identified or excluded by CTA. Early treatment and prevention of disease progression are more beneficial to patients.

Experimental aortic aneurysm severity and growth depend on topical elastase concentration and lysyl oxidase inhibition

Abdominal aortic aneurysm (AAA) formation and expansion is highly complex and multifactorial, and the improvement of animal models is an important step to enhance our understanding of AAA pathophysiology. In this study, we explore our ability to influence aneurysm growth in a topical elastase plus β-Aminopropionitrile (BAPN) mouse model by varying elastase concentration and by altering the cross-linking capability of the tissue. To do so, we assess both chronic and acute effects of elastase concentration using volumetric ultrasound. Our results suggest that the applied elastase concentration affects initial elastin degradation, as well as long-term vessel expansion. Additionally, we assessed the effects of BAPN by (1) removing it to restore the cross-linking capability of tissue after aneurysm formation and (2) adding it to animals with stable aneurysms to interrupt cross-linking. These results demonstrate that, even after aneurysm formation, lysyl oxidase inhibition remains necessary for continued expansion. Removing BAPN reduces the aneurysm growth rate to near zero, resulting in a stable aneurysm. In contrast, adding BAPN causes a stable aneurysm to expand. Altogether, these results demonstrate the ability of elastase concentration and BAPN to modulate aneurysm growth rate and severity. The findings open several new areas of investigation in a murine model that mimics many aspects of human AAA.

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.

CCN2 (Cellular Communication Network Factor 2) Deletion Alters Vascular Integrity and Function Predisposing to Aneurysm Formation

Background: CCN2 (cellular communication network factor 2) is a matricellular protein involved in cell communication and microenvironmental signaling responses. CCN2 is known to be overexpressed in several cardiovascular diseases, but its role is not completely understood. Methods: Here, CCN2 involvement in aortic wall homeostasis and response to vascular injury was investigated in inducible Ccn2 -deficient mice, with induction of vascular damage by infusion of Ang II (angiotensin II; 15 days), which is known to upregulate CCN2 expression in the aorta. Results: Ang II infusion in CCN2-silenced mice lead to 60% mortality within 10 days due to rapid development and rupture of aortic aneurysms, as evidenced by magnetic resonance imaging, echography, and histological examination. Ccn2 deletion decreased systolic blood pressure and caused aortic structural and functional changes, including elastin layer disruption, smooth muscle cell alterations, augmented distensibility, and increased metalloproteinase activity, which were aggravated by Ang II administration. Gene ontology analysis of RNA sequencing data identified aldosterone biosynthesis as one of the most enriched terms in CCN2-deficient aortas. Consistently, treatment with the mineralocorticoid receptor antagonist spironolactone before and during Ang II infusion reduced aneurysm formation and mortality, underscoring the importance of the aldosterone pathway in Ang II–induced aorta pathology. Conclusions: CCN2 is critically involved in the functional and structural homeostasis of the aorta and in maintenance of its integrity under Ang II–induced stress, at least, in part, by disruption of the aldosterone pathway. Thus, this study opens new avenues to future studies in disorders associated to vascular pathologies.

Ten-Year Experience in the Treatment of Coarctation of the Aorta through Endovascular Stenting in Patients of Different Age Groups

The aim. To analyze the 10-year experience in aortic coarctation endovascular stenting in patients of different age groups. Materials and methods. Examination and endovascular treatment of 194 patients aged 3 days to 60 years with coarctation of the aorta (CoA) with different anatomical and morphological variants was performed. According to the age criterion, the examined patients were divided into 4 study groups. The first group consisted of 84 patients (43.3%) over 25 years of age, group 2 included 33 patients (17.0%) aged 19 to 25 years, group 3 included 71 patients (36.6%) aged 5 to 18 years, and group 4 included 6 patients (3.1%) under 1 year of age. Results and discussion. We presented the clinical features of different anatomical and morphological variants of CoA. Endovascular treatment of CoA with stenting is considered the best method for adolescents and adults, due to the lower risk of aneurysm formation compared to balloon angioplasty. We were able to successfully reduce the invasive pressure gradient in patients of different ages and to establish the dependence of complication rate on the stent type used. The most common complications were aneurysm formation (2.1%) and stent migration (2.1%). Complications occurred more often in cases of uncovered stents compared to stent grafts (5.3% and 2.1%, respectively, p <0.05). No cases of hospital mortality were recorded in patients older than 5 years. Seven endovascular procedures were performed in 5 patients aged 3 days to 11 months (mean age 3.5 ± 1.6 months) with combined heart defects. Complications were documented in 1 child (20.0%). Endovascular intervention in pregnant women is indicated in refractory hypertension. We performed endovascular CoA stenting in 4 pregnant women at 15–23 weeks of gestation (average, 19.8 ± 3.1 weeks), and in 6 women with well-controlled hypertension stenting was performed within 48 hours to 5 years after delivery. In all the presented cases, successful revascularization was achieved. During follow-up (from 2 months to 10 years), all 10 women are alive, did not develop recoarctation or complications. Conclusions. The results of the analysis of CoA endovascular treatment showed that the chosen method and technique of intervention is appropriate and safe for patients of all ages, including pregnant women. Based on the results obtained, we have developed an algorithm for the management of patients who, according to clinical examination and echocardiography, were diagnosed with CoA during pregnancy.