Arteriosclerosis, thrombosis, and vascular biology
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Arterioscler. Thromb. Vasc. Biol. · Dec 2015
Epac1 Deficiency Attenuated Vascular Smooth Muscle Cell Migration and Neointimal Formation.
Vascular smooth muscle cell (SMC) migration causes neointima, which is related to vascular remodeling after mechanical injury and atherosclerosis development. We previously reported that an exchange protein activated by cAMP (Epac) 1 was upregulated in mouse arterial neointima and promoted SMC migration. In this study, we examined the molecular mechanisms of Epac1-induced SMC migration and the effect of Epac1 deficiency on vascular remodeling in vivo. ⋯ These data suggest that Epac1 deficiency attenuates neointima formation through, at least in part, inhibition of SMC migration, in which a decrease in Ca(2+) influx and a suppression of cofilin-mediated lamellipodia formation occur.
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Arterioscler. Thromb. Vasc. Biol. · Nov 2015
Comparative StudyDistinct First Trimester Cytokine Profiles for Gestational Hypertension and Preeclampsia.
Gestational hypertension and preeclampsia involve dysregulated maternal inflammatory responses to pregnancy, but whether such responses differ between the disorders has not been determined. We aimed to investigate disease-specific early pregnancy serum cytokine profiles of women subsequently developing gestational hypertension or preeclampsia for new insight into the underlying pathogeneses and differences between the disorders. ⋯ This study identifies early pregnancy differences in serum cytokine profiles for gestational hypertension and preeclampsia.
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Arterioscler. Thromb. Vasc. Biol. · Nov 2015
ReviewNonstatin Low-Density Lipoprotein-Lowering Therapy and Cardiovascular Risk Reduction-Statement From ATVB Council.
Pharmacological reduction of low-density lipoprotein (LDL) cholesterol using statin drugs is foundational therapy to reduce cardiovascular disease (CVD) risk. Here, we consider the place of nonstatin therapies that also reduce LDL cholesterol in prevention of CVD. Among conventional nonstatins, placebo-controlled randomized clinical trials showed that bile acid sequestrants, niacin, and fibrates given as monotherapy each reduce CVD end points. ⋯ Other nonstatin agents recently approved in the United States include lomitapide and mipomersen, which both act via distinctive LDL receptor independent mechanisms to substantially reduce LDL cholesterol in homozygous familial hypercholesterolemia. We also address some unanswered questions, including measuring alternative biochemical variables to LDL cholesterol, evidence for treating children with monitoring of subclinical atherosclerosis, and potential risks of extremely low LDL cholesterol. As evidence for benefit in CVD prevention accumulates, we anticipate that clinical practice will shift toward more assertive LDL-lowering treatment, using both statins and nonstatins initiated earlier in appropriately selected patients.
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Arterioscler. Thromb. Vasc. Biol. · Nov 2015
Potential for Recombinant ADAMTS13 as an Effective Therapy for Acquired Thrombotic Thrombocytopenic Purpura.
The metalloprotease ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) regulates the size of von Willebrand factor multimers. A deficiency in ADAMTS13 activity is associated with the life-threatening disease thrombotic thrombocytopenic purpura (TTP). The vast majority of patients have acquired TTP, where circulating anti-ADAMTS13 autoantibodies are causative for the decreased ADAMTS13 activity. Current treatment consists of plasma exchange, but improved therapies are highly warranted. ⋯ Recombinant ADAMTS13 was shown to be effective in averting severe acquired TTP-like symptoms in rats and holds promising value for the treatment of this severe and life-threatening disease in humans.
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Arterioscler. Thromb. Vasc. Biol. · Oct 2015
Comparative StudySleep Duration, Sleep Quality, and Markers of Subclinical Arterial Disease in Healthy Men and Women.
Short and long sleep duration are associated with increased risk of clinical cardiovascular events, but the association between sleep duration and subclinical cardiovascular disease is not well established. We examined the association between sleep duration and sleep quality with coronary artery calcification (CAC) and with brachial-ankle pulse wave velocity (PWV) in a large sample of young and middle-aged asymptomatic adults. ⋯ In this large study of apparently healthy men and women, extreme sleep duration and poor subjective sleep quality were associated with increased prevalence of CAC and higher PWV. Our results underscore the importance of an adequate quantity and quality of sleep to maintain cardiovascular health.