Circulation research
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Circulation research · Mar 2019
Selective BMP-9 Inhibition Partially Protects Against Experimental Pulmonary Hypertension.
Although many familial cases of pulmonary arterial hypertension exhibit an autosomal dominant mode of inheritance with the majority having mutations in essential constituents of the BMP (bone morphogenetic protein) signaling, the specific contribution of the long-term loss of signal transduction triggered by the BMPR2 (type 2 BMP receptor) remains poorly characterized. ⋯ Taken together, our data indicate that the loss of BMP9, by deletion or inhibition, has beneficial effects against pulmonary hypertension onset and progression.
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Circulation research · Mar 2019
Molecular Imaging Visualizes Recruitment of Inflammatory Monocytes and Macrophages to the Injured Heart.
Paradigm shifting studies have revealed that the heart contains functionally diverse populations of macrophages derived from distinct embryonic and adult hematopoietic progenitors. Under steady-state conditions, the heart is largely populated by CCR2- (C-C chemokine receptor type 2) macrophages of embryonic descent. After tissue injury, a dramatic shift in macrophage composition occurs whereby CCR2+ monocytes are recruited to the heart and differentiate into inflammatory CCR2+ macrophages that contribute to heart failure progression. Currently, there are no techniques to noninvasively detect CCR2+ monocyte recruitment into the heart and thus identify patients who may be candidates for immunomodulatory therapy. ⋯ These findings demonstrate the sensitivity and specificity of 68Ga-DOTA-ECL1i in the mouse heart and highlight the translational potential of this agent to noninvasively visualize CCR2+ monocyte recruitment and inflammatory macrophage accumulation in patients.
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Circulation research · Mar 2019
High-Risk Human Papillomavirus Infection and the Risk of Cardiovascular Disease in Korean Women.
Until now, no cohort studies have evaluated the relationship between high-risk human papillomavirus (HPV) infection and new-onset cardiovascular diseases (CVD). ⋯ In this large cohort, high-risk HPV infection was significantly associated with an increased risk of developing CVD, especially in obese individuals and those with MetS, indicating that high-risk HPV might affect CVD risk with possible effect modification by obesity and MetS.
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Circulation research · Mar 2019
Comparative StudyDietary Fats in Relation to Total and Cause-Specific Mortality in a Prospective Cohort of 521 120 Individuals With 16 Years of Follow-Up.
Evidence linking saturated fat intake with cardiovascular health is controversial. The associations of unsaturated fats with total and cardiovascular disease (CVD) mortality remain inconsistent, and data about non-CVD mortality are limited. ⋯ URL: http://www.clinicaltrials.gov . Unique identifier: NCT00340015.
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Circulation research · Feb 2019
ReviewAnticytokine Agents: Targeting Interleukin Signaling Pathways for the Treatment of Atherothrombosis
The recognition that atherosclerosis is a complex chronic inflammatory disorder mediated through both adaptive and innate immunity has led to the hypothesis that anticytokine therapies targeting specific IL (interleukin) signaling pathways could serve as powerful adjuncts to lipid lowering in the prevention and treatment of cardiovascular disease. Cytokines involved in human atherosclerosis can be broadly classified as proinflammatory and proatherogenic (such as IL-1, IL-6, and TNF [tumor necrosis factor]) or as anti-inflammatory and antiatherogenic (such as IL-10 and IL-1rA). The recent CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) has shown that specific targeting of IL-1β can significantly reduce cardiovascular event rates without lipid or blood pressure lowering. ⋯ By contrast, in the recent CIRT (Cardiovascular Inflammation Reduction Trial), low-dose methotrexate neither reduced IL-1β, IL-6, or high-sensitivity CRP nor lowered cardiovascular event rates. Taken together, these 2 contemporary trials provide proof of principle that focused cytokine inhibition, not broad-spectrum anti-inflammatory therapy, is likely to be crucial for atheroprotection. This review provides an overview of cytokines in atherosclerosis, the potential benefits and risks associated with targeted anticytokine therapies, and a look to the future of clinical practices addressing residual inflammatory risk.