Redox Regulation of the Microcirculation.

The microcirculation maintains tissue homeostasis through local regulation of blood flow and oxygen delivery. Perturbations in microvascular function are characteristic of several diseases and may be early indicators of pathological changes in the cardiovascular system and in parenchymal tissue function. These changes are often mediated by various reactive oxygen species and linked to disruptions in pathways such as vasodilation or angiogenesis.

Lysophosphatidic acid acts on LPA receptor to increase H O during flow-induced dilation in human adipose arterioles.

Background And Purpose: NO produces arteriolar flow-induced dilation (FID) in healthy subjects but is replaced by mitochondria-derived hydrogen peroxide (mtH O ) in patients with coronary artery disease (CAD). Lysophosphatidic acid (LPA) is elevated in patients with risk factors for CAD, but its functional effect in arterioles is unknown. We tested whether elevated LPA changes the mediator of FID from NO to mtH O in human visceral and subcutaneous adipose arterioles.

Physiological Consequences of Coronary Arteriolar Dysfunction and Its Influence on Cardiovascular Disease.

To date, the major focus of diagnostic modalities and interventions to treat coronary artery disease has been the large epicardial vessels. Despite substantial data showing that microcirculatory dysfunction is a strong predictor of future adverse cardiovascular events, very little research has gone into developing techniques for in vivo diagnosis and therapeutic interventions to improve microcirculatory function. In this review, we will discuss the pathophysiology of coronary arteriolar dysfunction, define its prognostic implications, evaluate the diagnostic modalities available, and provide speculation on current and potential therapeutic opportunities.

Telomerase reverse transcriptase protects against angiotensin II-induced microvascular endothelial dysfunction.

A rise in reactive oxygen species (ROS) may contribute to cardiovascular disease by reducing nitric oxide (NO) levels, leading to loss of NO's vasodilator and anti-inflammatory effects. Although primarily studied in larger conduit arteries, excess ROS release and a corresponding loss of NO also occur in smaller resistance arteries of the microcirculation, but the underlying mechanisms and therapeutic targets have not been fully characterized. We examined whether either of the two subunits of telomerase, telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC), affect microvascular ROS production and peak vasodilation at baseline and in response to in vivo administration to angiotensin II (ANG II).

Microvascular Adaptations to Exercise: Protective Effect of PGC-1 Alpha.

Background: Sedentary behavior and obesity are major risk factors for cardiovascular disease. Regular physical activity has independent protective effects on the cardiovascular system, but the mechanisms responsible remain elusive. Recent studies suggest that the protein peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) participates in the response to exercise training.

PGC-1α (Peroxisome Proliferator-Activated Receptor γ Coactivator 1-α) Overexpression in Coronary Artery Disease Recruits NO and Hydrogen Peroxide During Flow-Mediated Dilation and Protects Against Increased Intraluminal Pressure.

Blood flow through healthy human vessels releases NO to produce vasodilation, whereas in patients with coronary artery disease (CAD), the mediator of dilation transitions to mitochondria-derived hydrogen peroxide (HO). Excessive HO production contributes to a proatherosclerotic vascular milieu. Loss of PGC-1α (peroxisome proliferator-activated receptor γ coactivator 1α) is implicated in the pathogenesis of CAD.

Hypertension during Weight Lifting Reduces Flow-Mediated Dilation in Nonathletes.

Purpose: The purpose of this study was to determine whether increased intraluminal pressure is the damaging factor that reduces flow-mediated dilation (FMD) in young, healthy subjects after resistance exercise to maximal exertion.

Hypothesis: Attenuating the rise in brachial artery pressure during weight lifting by placing a blood pressure cuff on the upper arm prevents postexercise impairment of brachial artery FMD in sedentary individuals.

Methods: Nine sedentary individuals who exercise once a week or less and six exercise-trained individuals who exercise three times a week or more performed leg press exercise to maximal exertion on two separate occasions.

Friend or foe? Telomerase as a pharmacological target in cancer and cardiovascular disease.

Aging, cancer, and chronic disease have remained at the forefront of basic biological research for decades. Within this context, significant attention has been paid to the role of telomerase, the enzyme responsible for lengthening telomeres, the nucleotide sequences located at the end of chromosomes found in the nucleus. Alterations in telomere length and telomerase activity are a common denominator to the underlying pathology of these diseases.

Role of PGC-1α in Vascular Regulation: Implications for Atherosclerosis.

Mitochondrial dysfunction results in high levels of oxidative stress and mitochondrial damage, leading to disruption of endothelial homeostasis. Recent discoveries have clarified several pathways, whereby mitochondrial dysregulation contributes to endothelial dysfunction and vascular disease burden. One such pathway centers around peroxisome proliferator receptor-γ coactivator 1α (PGC-1α), a transcriptional coactivator linked to mitochondrial biogenesis and antioxidant defense, among other functions.

Mitochondrial signaling in the vascular endothelium: beyond reactive oxygen species.

Traditionally, the mitochondria have been viewed as the cell's powerhouse, producing energy in the form of ATP. As a byproduct of ATP formation, the mitochondrial electron transport chain produces substantial amounts of reactive oxygen species (ROS). First thought to be toxic, recent literature indicates an important signaling function for mitochondria-derived ROS, especially in relation to cardiovascular disease pathogenesis.

The Human Microcirculation: Regulation of Flow and Beyond.

The microcirculation is responsible for orchestrating adjustments in vascular tone to match local tissue perfusion with oxygen demand. Beyond this metabolic dilation, the microvasculature plays a critical role in modulating vascular tone by endothelial release of an unusually diverse family of compounds including nitric oxide, other reactive oxygen species, and arachidonic acid metabolites. Animal models have provided excellent insight into mechanisms of vasoregulation in health and disease.