Arteriosclerosis, thrombosis, and vascular biology
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Arterioscler. Thromb. Vasc. Biol. · Aug 2017
Blood Pressure and Heart Rate Measures Associated With Increased Risk of Covert Brain Infarction and Worsening Leukoaraiosis in Older Adults.
In people without previous stroke, covert findings on serial magnetic resonance imaging (MRI) of incident brain infarcts and worsening leukoaraiosis are associated with increased risk for ischemic stroke and dementia. We evaluated whether various measures of blood pressure (BP) and heart rate are associated with these MRI findings. ⋯ Elevated mean systolic BP is associated with increased risk for covert brain infarction, and elevated mean diastolic BP is associated with increased risk for worsening leukoaraiosis. These findings reinforce the importance of hypertension in the development of silent cerebrovascular diseases, but the pathophysiologic relationships to BP for each may differ.
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Arterioscler. Thromb. Vasc. Biol. · Aug 2017
Human Blood Monocyte Subsets: A New Gating Strategy Defined Using Cell Surface Markers Identified by Mass Cytometry.
Human monocyte subsets are defined as classical (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical (CD14+CD16+). Alterations in monocyte subset frequencies are associated with clinical outcomes, including cardiovascular disease, in which circulating intermediate monocytes independently predict cardiovascular events. However, delineating mechanisms of monocyte function is hampered by inconsistent results among studies. ⋯ Using cytometry by time-of-flight mass cytometry, we have identified a small panel of surface markers that can significantly improve monocyte subset identification and purity in flow cytometry. Such a revised gating scheme will be useful for clinical studies of monocyte function in human cardiovascular disease.
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Arterioscler. Thromb. Vasc. Biol. · Aug 2017
Codependence of Bone Morphogenetic Protein Receptor 2 and Transforming Growth Factor-β in Elastic Fiber Assembly and Its Perturbation in Pulmonary Arterial Hypertension.
We determined in patients with pulmonary arterial (PA) hypertension (PAH) whether in addition to increased production of elastase by PA smooth muscle cells previously reported, PA elastic fibers are susceptible to degradation because of their abnormal assembly. ⋯ Disrupting BMPR2 impairs TGFβ1- and BMP4-mediated elastic fiber assembly and is of pathophysiologic significance in PAH.
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Arterioscler. Thromb. Vasc. Biol. · Aug 2017
Implication of Inflammation and Epigenetic Readers in Coronary Artery Remodeling in Patients With Pulmonary Arterial Hypertension.
Pulmonary arterial hypertension (PAH) is a vascular disease not restricted to the lungs. Many signaling pathways described in PAH are also of importance in other vascular remodeling diseases, such as coronary artery disease (CAD). Intriguingly, CAD is 4× more prevalent in PAH compared with the global population, suggesting a link between these 2 diseases. Both PAH and CAD are associated with sustained inflammation and smooth muscle cell proliferation/apoptosis imbalance and we demonstrated in PAH that this phenotype is, in part, because of the miR-223/DNA damage/Poly[ADP-ribose] polymerase 1/miR-204 axis activation and subsequent bromodomain protein 4 (BRD4) overexpression. Interestingly, BRD4 is also a trigger for calcification and remodeling processes, both of which are important in CAD. Thus, we hypothesize that BRD4 activation in PAH influences the development of CAD. ⋯ Overall, this study demonstrates that increased BRD4 expression in coronary arteries of patient with PAH contributes to vascular remodeling and comorbidity development.