Calcification of the thoracic aorta on low-dose chest CT predicts severe COVID-19.

BACKGROUND: Cardiovascular comorbidity anticipates poor prognosis of SARS-CoV-2 disease (COVID-19) and correlates with the systemic atherosclerotic transformation of the arterial vessels. The amount of aortic wall calcification (AWC) can be estimated on low-dose chest CT. We suggest quantification of AWC on the low-dose chest CT, which is initially performed for the diagnosis of COVID-19, to screen for patients at risk of severe COVID-19. METHODS: Seventy consecutive patients (46 in center 1, 24 in center 2) with parallel low-dose chest CT and positive RT-PCR for SARS-CoV-2 were included in our multi-center, multi-vendor study. The outcome was rated moderate (no hospitalization, hospitalization) and severe (ICU, tracheal intubation, death), the latter implying a requirement for intensive care treatment. The amount of AWC was quantified with the CT vendor's software. RESULTS: Of 70 included patients, 38 developed a moderate, and 32 a severe COVID-19. The average volume of AWC was significantly higher throughout the subgroup with severe COVID-19, when compared to moderate cases (771.7 mm3 (Q1 = 49.8 mm3, Q3 = 3065.5 mm3) vs. 0 mm3 (Q1 = 0 mm3, Q3 = 57.3 mm3)). Within multivariate regression analysis, including AWC, patient age and sex, as well as a cardiovascular comorbidity score, the volume of AWC was the only significant regressor for severe COVID-19 (p = 0.004). For AWC > 3000 mm3, the logistic regression predicts risk for a severe progression of 0.78. If there are no visually detectable AWC risk for severe progression is 0.13, only. CONCLUSION: AWC seems to be an independent biomarker for the prediction of severe progression and intensive care treatment of COVID-19 already at the time of patient admission to the hospital; verification in a larger multi-center, multi-vendor study is desired.

Targeted gene expression analyses and immunohistology suggest a pro-proliferative state in tricuspid aortic valve-, and senescence and viral infections in bicuspid aortic valve-associated thoracic aortic aneurysms.

BACKGROUND AND AIMS: Despite the potential life-threatening consequences of thoracic aortic aneurysms (TAAs), the pathogenesis of these diseases is still poorly understood. While some aspects of TAA formation have been elucidated, the role of vascular smooth muscle cells (SMCs) in both bicuspid aortic valve (BAV)-associated and degenerative tricuspid aortic valve (TAV)-associated TAAs has not yet been fully unravelled. Thus, this work was aimed at uncovering processes in SMC biology that may contribute to TAA formation. METHODS: Using isolated SMCs and tissue samples from TAAs linked to BAV syndrome, TAV-associated degenerative TAAs and control aortas, we performed targeted mRNA expression profile analyses and conducted immunohistological analyses on aortic wall tissue sections. RESULTS: While SMC expression profiles and tissue analyses in TAV-TAAs clearly point toward a pro-proliferative state of the aortic media SMCs, BAV-TAA SMCs and tissue provide evidence for DNA damage, DNA damage response signalling as well as profound TLR-3 signalling. CONCLUSIONS: The data presented in this study emphasizes the importance of SMCs in TAA development. Furthermore, our results provide evidence that the state of SMCs in the BAV-TAA (senescent) and TAV-TAA (pro-proliferative) differs significantly. For the first time, we also present findings that may argue for the occurrence of a viral infection in BAV-TAA SMCs.

Adeno-associated virus (AAV)-7 and -8 poorly transduce vascular endothelial cells and are sensitive to proteasomal degradation.

Transduction of the vascular endothelium by adeno-associated virus (AAV) vectors would have broad appeal for gene therapy. However, levels of transduction by AAV serotype-2 are low, an observation linked to deficiencies in endothelial cell binding, sequestration of virions in the extracellular matrix and/or virion degradation by the proteasome. Strategies to improve transduction of endothelial cells include AAV-2 capsid targeting using small peptides isolated by phage display or the use of alternate serotypes. Previously, we have shown that AAV serotypes-3 through -6 transduce endothelial cells with poor efficiency. Recently, AAV serotypes-7 and -8 have been shown to mediate efficient transduction of the skeletal muscle and liver, respectively, although their infectivity profile for vascular cells has not been addressed. Here, we show that AAV-7 and -8 also transduce endothelial cells with poor efficiency and the levels of transgene expression are markedly enhanced by inhibition of the proteasome. In both cases proteasome blockade enhances the nuclear translocation of virions. We further show that this is vascular cell-type selective since transduction of smooth muscle cells is not sensitive to proteasome inhibition. Analysis in intact blood vessels corroborated these findings and suggests that proteasome degradation is a common limiting factor for endothelial cell transduction by AAV vectors.

Histological lesions in vascular tissues of bovine herpes virus type 4-infected rabbits.

The gamma-herpes virus bovine herpes virus type 4 (BoHV-4) is distributed worldwide in cattle populations with unknown pathogenicity. Bovine endothelial cells were recently shown to be susceptible to BoHV-4 infection in vitro and this virus accelerated the cholesterol-induced atherosclerotic process in rabbits. In this study, the in vivo effect of BoHV-4 on cardiovascular tissue was investigated by intravenous infection of rabbits fed a cholesterol free diet. Inflammatory lesions of vascular tissue in aortic and valvular endothelial cells, and smooth muscle cells were detected by H&E staining, PCR, IF, EM immunohistochemistry, while virus isolation was used to detect virus particles. Acute and chronic vasculitis, signs of chronic endocarditis, with mononuclear cell accumulation and a fresh thrombus was found. Herpes viruses have already been thought to initiate cardio-vascular disorders, now this paper shows that a bovine gamma-herpes virus could also be a causative agent of vascular lesions in mammals fed a normal diet. BoHV-4-infection of rabbits could serve as a useful animal model for research into virus-induced human cardio-vascular diseases.

Expression of secretory group IIA phospholipase A(2) in relation to the presence of microbial agents, macrophage infiltrates, and transcripts of proinflammatory cytokines in human aortic tissues.

Recent seroepidemiological and immunohistochemical studies have demonstrated an association between microbial infections and atherosclerosis. However, the mechanisms underlying this association are widely unknown. In the present study, arterial specimens obtained at autopsy after sudden death were analyzed concerning (1) the presence of Chlamydia pneumoniae, cytomegalovirus, herpes simplex virus, and Helicobacter pylori; (2) the expression of secretory group IIA phospholipase A(2) (sPLA(2)-IIA) and of proinflammatory cytokines; and (3) the stage of atherosclerosis. Genomic DNA of microbial pathogens was determined by the polymerase chain reaction technique. The expression of sPLA(2)-IIA was studied immunohistochemically by using monoclonal antibodies against human sPLA(2)-IIA. Transcripts specific for sPLA(2)-IIA, interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma were identified by reverse transcription-polymerase chain reaction. In 18 of 102 analyzed specimens, DNA of microbial pathogens was found. Thirteen sections were positive for C pneumoniae, whereas 2 specimens were positive either for cytomegalovirus or for herpes simplex virus. One section contained genomic DNA of all 3 pathogens simultaneously. None of the analyzed tissues exhibited nucleic acids specific for H pylori. In addition to macrophage infiltrates, the presence of microbial DNA was closely associated with the occurrence of transcripts specific for proinflammatory cytokines and sPLA(2)-IIA. Pathogens as well as sPLA(2)-IIA and cytokines were found to be present not only in advanced but also in early stages of atherosclerosis. In tissues negative for sPLA(2)-IIA and cytokine expression, none of the pathogens could be identified. Because macrophages exposed to phospholipase A(2)-treated lipoproteins are transformed into foam cells in vitro, the results of this study suggest an alternative mechanism by which microbial infections may act in a proatherogenic fashion in vessel walls.