Arteriosclerosis, thrombosis, and vascular biology
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Arterioscler. Thromb. Vasc. Biol. · Jan 2021
Human Aortic Valve Interstitial Cells Display Proangiogenic Properties During Calcific Aortic Valve Disease.
The study's aim was to analyze the capacity of human valve interstitial cells (VICs) to participate in aortic valve angiogenesis. Approach and Results: VICs were isolated from human aortic valves obtained after surgery for calcific aortic valve disease and from normal aortic valves unsuitable for grafting (control VICs). We examined VIC in vitro and in vivo potential to differentiate in endothelial and perivascular lineages. VIC paracrine effect was also examined on human endothelial colony-forming cells. A pathological VIC (VICp) mesenchymal-like phenotype was confirmed by CD90+/CD73+/CD44+ expression and multipotent-like differentiation ability. When VICp were cocultured with endothelial colony-forming cells, they formed microvessels by differentiating into perivascular cells both in vivo and in vitro. VICp and control VIC conditioned media were compared using serial ELISA regarding quantification of endothelial and angiogenic factors. Higher expression of VEGF (vascular endothelial growth factor)-A was observed at the protein level in VICp-conditioned media and confirmed at the mRNA level in VICp compared with control VIC. Conditioned media from VICp induced in vitro a significant increase in endothelial colony-forming cell proliferation, migration, and sprouting compared with conditioned media from control VIC. These effects were inhibited by blocking VEGF-A with blocking antibody or siRNA approach, confirming VICp involvement in angiogenesis by a VEGF-A dependent mechanism. ⋯ We provide here the first proof of an angiogenic potential of human VICs isolated from patients with calcific aortic valve disease. These results point to a novel function of VICp in valve vascularization during calcific aortic valve disease, with a perivascular differentiation ability and a VEGF-A paracrine effect. Targeting perivascular differentiation and VEGF-A to slow calcific aortic valve disease progression warrants further investigation.
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Arterioscler. Thromb. Vasc. Biol. · Dec 2020
Editorial CommentMegakaryocytes: Masters of Innate Immunity?
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Arterioscler. Thromb. Vasc. Biol. · Nov 2020
Comparative StudyCOVID-19 in the Healthy Patient Population: Demographic and Clinical Phenotypic Characterization and Predictors of In-Hospital Outcomes.
Coronavirus disease 2019 (COVID-19) can infect patients in any age group including those with no comorbid conditions. Understanding the demographic, clinical, and laboratory characteristics of these patients is important toward developing successful treatment strategies. Approach and Results: In a retrospective study design, consecutive patients without baseline comorbidities hospitalized with confirmed COVID-19 were included. Patients were subdivided into ≤55 and >55 years of age. Predictors of in-hospital mortality or mechanical ventilation were analyzed in this patient population, as well as subgroups. Stable parameters in overall and subgroup models were used to construct a cluster model for phenotyping of patients. Of 1207 COVID-19-positive patients, 157 met the study criteria (80≤55 and 77>55 years of age). Most reliable predictors of outcomes overall and in subgroups were age, initial and follow-up d-dimer, and LDH (lactate dehydrogenase) levels. Their predictive cutoff values were used to construct a cluster model that produced 3 main clusters. Cluster 1 was a low-risk cluster and was characterized by younger patients who had low thrombotic and inflammatory features. Cluster 2 was intermediate risk that also consisted of younger population that had moderate level of thrombosis, higher inflammatory cells, and inflammatory markers. Cluster 3 was a high-risk cluster that had the most aggressive thrombotic and inflammatory feature. ⋯ In healthy patient population, COVID-19 remains significantly associated with morbidity and mortality. While age remains the most important predictor of in-hospital outcomes, thromboinflammatory interactions are also associated with worse clinical outcomes regardless of age in healthy patients.
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Arterioscler. Thromb. Vasc. Biol. · Nov 2020
Comparative Study Observational StudyHigh-Mobility Group Box-1 Is Associated With Obesity, Inflammation, and Subclinical Cardiovascular Risk Among Young Adults: A Longitudinal Cohort Study.
We aimed to characterize circulating HMGB1 (high-mobility group box-1) levels, one of the better-characterized damage-associated molecular patterns, with respect to age, sex, and race in the general population, and investigate the longitudinal associations of HMGB1 with inflammatory markers, obesity, and preclinical markers of cardiovascular disease. Approach and Results: The analyses included 489 participants (50% Blacks, aged 24.6±3.3 years at the first visit) with up to 4 follow-up visits (1149 samples) over a maximum of 8.5 years. Systolic blood pressure, diastolic blood pressure, carotid-femoral pulse wave velocity, and carotid intima-media thickness together with plasma HMGB1, hs-CRP (high-sensitivity C-reactive protein), IFN-γ (interferon-γ), IL-6 (interleukin-6), IL-10 (interleukin-10), and TNF-α (tumor necrosis factor-α) were measured at each visit. At baseline, plasma HMGB1 concentrations were higher in Blacks compared with Whites (3.86 versus 3.20 ng/mL, P<0.001), and in females compared with males (3.75 versus 3.30 ng/mL, P=0.005). HMGB1 concentrations increased with age (P=0.007), and higher levels of obesity measures (P<0.001). Without adjustment for age, sex, race, and body mass index, HMGB1 concentrations were positively associated with hs-CRP, IL-6, TNF-α, systolic blood pressure, diastolic blood pressure, and carotid-femoral pulse wave velocity (P<0.05) but not IL-10, IFN-γ or carotid intima-media thickness. After covariate adjustments, the associations of HMGB1 with hs-CRP, and carotid-femoral pulse wave velocity remained statistically significant (P<0.05). ⋯ This study demonstrates the age, sex, and race differences in circulating HMGB1. The increasing circulating concentrations of HMGB1 with age suggest a potential role of HMGB1 in the pathogenesis of chronic low-grade inflammation, obesity, and subclinical cardiovascular disease risk.
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Arterioscler. Thromb. Vasc. Biol. · Nov 2020
ReviewCOVID-19 and Respiratory System Disorders: Current Knowledge, Future Clinical and Translational Research Questions.
The severe acute respiratory syndrome coronavirus-2 emerged as a serious human pathogen in late 2019, causing the disease coronavirus disease 2019 (COVID-19). The most common clinical presentation of severe COVID-19 is acute respiratory failure consistent with the acute respiratory distress syndrome. Airway, lung parenchymal, pulmonary vascular, and respiratory neuromuscular disorders all feature in COVID-19. This article reviews what is known about the effects of severe acute respiratory syndrome coronavirus-2 infection on different parts of the respiratory system, clues to understanding the underlying biology of respiratory disease, and highlights current and future translation and clinical research questions.