Perivascular Fat and the Microcirculation: Relevance to Insulin Resistance, Diabetes, and Cardiovascular Disease

Type 2 diabetes and its major risk factor, obesity, are a growing burden for public health. The mechanisms that connect obesity and its related disorders, such as insulin resistance, type 2 diabetes, and hypertension, are still undefined. Microvascular dysfunction may be a pathophysiologic link between insulin resistance and hypertension in obesity. Many studies have shown that adipose tissue-derived substances (adipokines) interact with (micro)vascular function and influence insulin sensitivity. In the past, research focused on adipokines from perivascular adipose tissue (PVAT). In this review, we focus on the interactions between adipokines, predominantly from PVAT, and microvascular function in relation to the development of insulin resistance, diabetes, and cardiovascular disease

Effect of Resveratrol-Based Nutritional Supplement on Choroidal Thickness: A Pilot Study

PurposeThe effect of an oral trans-resveratrol-based supplement (Longevinex®) on choroidal thickness, measured using optical coherence tomography (OCT) enhanced depth imaging, was investigated in a prospective study.Materials and methods34 young, healthy participants were randomly divided into two age- and gender-matched groups. They were then assigned in a randomized fashion to treat with either a trans-resveratrol-based group (Longevinex®, Las Vegas) or placebo. All participants underwent ocular imaging with spectral domain (SD)-OCT (Spectralis; Heidelberg Engineering, Heidelberg) at the baseline and then again 1 h following treatment. The choroidal thickness was measured in a masked fashion at the fovea and at four additional points, located at 500 μm and 1000 μm nasal to the fovea and 500 μm and 1000 μm temporal to the fovea.ResultsIn the resveratrol group, the foveal choroidal thickness at the baseline was 267.73 ± 84.19 μm (mean ± SD); it increased to 284.57 ± 92.39 μm 1 h after drug treatment (p = 0.033). The mean choroidal thickness was also significantly increased at each of the four extrafoveal points (all p < 0.05). In the control group, the mean baseline choroidal thickness at the fovea was 269.73 ± 71.40 μm (mean ± SD) and it was 268.43 ± 70.15 μm (mean ± SD) 1 h after the placebo was administered (p = 0.183); there were also no significant differences in choroidal thickness at the four additional points (all p > 0.05) Conclusion: A significant increase in choroidal thickness following oral administration of a trans-resveratrol-based supplement was observed. There was no change in choroidal thickness in the placebo-treated control group. We speculate that the increased choroidal thickness is the result of choroidal vessel vasodilation

Testing hypotheses of aging in long-lived mice of the genus Peromyscus: association between longevity and mitochondrial stress resistance, ROS detoxification pathways, and DNA repair efficiency

In the present review we discuss the potential use of two long-lived mice of the genus Peromyscus—the white-footed mouse (P. leucopus) and the deer mouse (P. maniculatus) maximum lifespan potential ∼8 years for both—to test predictions of theories about aging from the oxidative stress theory, mitochondrial theory and inflammatory theory. Previous studies have shown that P. leucopus cells exhibit superior antioxidant defense mechanisms and lower cellular production of reactive oxygen species (ROS) than do cells of the house mouse, Mus musculus (maximum lifespan ∼3.5 years). We present new data showing that mitochondria in P. leucopus cells produce substantially less ROS than mitochondria in M. musculus cells, and that P. leucopus mitochondria exhibit superior stress resistance to those of M. musculus. We also provide evidence that components of the DNA repair system (e.g., pathways involved in repair of DNA damage induced by γ-irradiation) are likely to be more efficient in P. leucopus than in M. musculus. We propose that mitochondrial stress resistance, ROS detoxification pathways and more efficient DNA repair contribute to the previously documented resistance of P. leucopus cells toward oxidative stress-induced apoptosis. The link between these three pathways and species longevity is discussed

Partial IGF-1 deficiency is sufficient to reduce heart contractibility, angiotensin II sensibility, and alter gene expression of structural and functional cardiac proteins

Circulating levels of IGF-1 may decrease under several circumstances like ageing, metabolic syndrome, and advanced cirrhosis. This reduction is associated with insulin resistance, dyslipidemia, progression to type 2 diabetes, and increased risk for cardiovascular diseases. However, underlying mechanisms between IGF-1 deficiency and cardiovascular disease remain elusive. The specific aim of the present work was to study whether the partial IGF-1 deficiency influences heart and/or coronary circulation, comparing vasoactive factors before and after of ischemia-reperfusion (I/R). In addition, histology of the heart was performed together with cardiac gene expression for proteins involved in structure and function (extracellular matrix, contractile proteins, active peptides); carried out using microarrays, followed by RT-qPCR confirmation of the three experimental groups. IGF-1 partial deficiency is associated to a reduction in contractility and angiotensin II sensitivity, interstitial fibrosis as well as altered expression pattern of genes involved in extracellular matrix proteins, calcium dynamics, and cardiac structure and function. Although this work is descriptive, it provides a clear insight of the impact that partial IGF-1 deficiency on the heart and establishes this experimental model as suitable for studying cardiac disease mechanisms and exploring therapeutic options for patients under IGF-1 deficiency conditions