Jane Titterington

IGF-1 Reduces Inflammatory Responses, Suppresses Oxidative Stress, and Decreases Atherosclerosis Progression in ApoE-Deficient Mice

Objective—Whereas growth factors, via their ability to stimulate vascular smooth muscle cell (VSMC) proliferation and migration, have been thought to play a permissive role in atherosclerosis initiation and progression, the role of insulin-like growth factor-1 (IGF-1) is unknown. Here we report for the first time that IGF-1 infusion decreased atherosclerotic plaque progression in ApoE-deficient mice on a Western diet. Methods and Results—ApoE-null mice (8 weeks) were infused with vehicle or recombinant human IGF-1 and fed a high-fat diet for 12 weeks. Analysis of aortic sinuses revealed that IGF-1 infusion decreased atherosclerotic plaque progression and macrophage infiltration into lesions. Furthermore, IGF-1 decreased vascular expression of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-α, reduced aortic superoxide formation and urinary 8-isoprostane levels, and increased aortic pAkt and eNOS expression and circulating endothelial progenitor cells, consistent with an antiinflammatory, antioxidant, and prorepair effect on the vasculature. Conclusions—Our data indicate that an increase in circulating IGF-1 reduces vascular inflammatory responses, systemic and vascular oxidant stress and decreases atherosclerotic plaque progression. These findings have major implications for the treatment of atherosclerosis.

Differential requirement for nitric oxide in IGF-1-induced anti-apoptotic, anti-oxidant and anti-atherosclerotic effects.

We have shown previously that insulin like‐growth factor I (IGF‐1) suppressed atherosclerosis in Apoe−/− mice and activated endothelial nitric oxide (NO) synthase. To determine whether IGF‐1‐induced atheroprotection depends on NO, IGF‐1‐ or saline‐infused mice were treated with l‐NAME, the pan‐NO synthase inhibitor or with d‐NAME (control). IGF‐1 reduced atherosclerosis in both the d‐NAME and l‐NAME groups suggesting that IGF‐1s anti‐atherogenic effect was NO‐independent. IGF‐1 increased plaque smooth muscle cells, suppressed cell apoptosis and downregulated lipoprotein lipase and these effects were also NO‐independent. On the contrary, IGF‐1 decreased oxidative stress and suppressed TNF‐α levels and these effects were blocked by l‐NAME. Thus IGF‐1s anti‐oxidant effect is dependent on its ability to increase NO but is distinct from its anti‐atherosclerotic effect which is NO‐independent.

Gender differences in acute coronary syndromes: focus on the women with ACS without an obstructing culprit lesion

ABSTRACT Introduction: The etiologies of acute coronary syndromes (ACS) in women expand beyond the traditional paradigm of obstructive epicardial atherosclerotic disease and plaque rupture. Fundamental differences in pathobiology and presentation can partially explain the gender disparity in ACS diagnosis and management, but there is also much we do not know about the spectrum of coronary artery disease in women. Areas covered: This review seeks to explain some key differences between men and women in terms of risk factors, pathophysiology, and clinical presentations, as well as identify areas where more data are needed, focusing on women presenting with ACS but without a culprit lesion to explain their presentation. Literature search was undertaken with PubMed and Google Scholar. Expert commentary: Women with acute coronary syndromes but without plaque rupture or obstructive epicardial atherosclerosis can be difficult to diagnose and manage. Improving care in this underdiagnosed and undertreated population will require early identification of at risk patients, development of better diagnostic strategies, and standardized implementation of guideline-based therapies.

Evolving cardiovascular care for women: a decade of progress

10.2217/FCA.15.24

A NOVEL IMAGING PROBE FOR THE DETECTION OF SUBCLINICAL BACTERIAL INFECTIONS INVOLVING CARDIAC DEVICES

Infection of implantable cardiac devices is a significant clinical entity that poses a diagnostic challenge. We have developed a novel approach to specifically detect bacteria using a fluorescent imaging probe. In bacteria unlike mammalian cells, maltohexaose is taken up as a major energy source. We