What is the central question of this study? Does passive heat stress of +2°C oesophageal temperature change concentrations of circulating arterial endothelial- and platelet-derived microparticles in healthy adults? What is the main finding and its importance? Concentrations of circulating endothelial- and platelet-derived microparticles were markedly decreased in heat stress. Reductions in circulating microparticles might indicate favourable vascular changes associated with non-pathological hyperthermia. Interest in circulating endothelial- and platelet-derived microparticles (EMPs and PMPs, respectively) has increased because of their potential pathogenic role in vascular disease and as biomarkers for vascular health. Hyperthermia is commonly associated with a pro-inflammatory stress but might also provide vascular protection when the temperature elevation is non-pathological. Circulating microparticles might contribute to the cellular adjustments and resultant vascular impacts of hyperthermia. Here, we determined whether circulating concentrations of arterial EMPs and PMPs are altered by passive heat stress (+2°C oesophageal temperature). Ten healthy young men (age 23 ± 3 years) completed the study. Hyperthermia was achieved by circulating ∼49°C water through a water-perfused suit that covered the entire body except the hands, feet and head. Arterial (radial) blood samples were obtained immediately before heating (normothermia) and in hyperthermia. The mean ± SD oesophageal temperature in normothermia was 37.2 ± 0.1°C and in hyperthermia 39.1 ± 0.1°C. Concentrations of circulating EMPs and PMPs were markedly decreased in hyperthermia. Activation-derived EMPs were reduced by ∼30% (mean ± SD; from 61 ± 8 to 43 ± 7 microparticles μl ; P < 0.05) and apoptosis-derived EMPs by ∼45% (from 46 ± 7 to 23 ± 3 microparticles μl ; P < 0.05). Likewise, circulating PMPs were reduced by ∼75% in response to hyperthermia (from 256 ± 43 to 62 ± 14 microparticles μl ). These beneficial reductions in circulating EMPs and PMPs in response to a 2°C increase in core temperature might partly underlie the reported vascular improvements following therapeutic bouts of physiological hyperthermia.

Background Cardiolipin, a unique phospholipid in the inner mitochondrial membrane, is critical for optimal mitochondrial function. CL abnormalities have been demonstrated in the failing rodent and adult human heart. The aim of this study was to determine whether abnormalities in CL content and the CL biosynthesis and remodeling pathways are present in pediatric idiopathic dilated cardiomyopathy (IDC). Methods and Results A cross-sectional analysis of myocardial tissue from 119 IDC and non-failing (NF) control samples was performed. Electrospray ionizing mass spectrometry was used to measure total CL and CL species content in LV tissue. RT-PCR was employed to measure gene expression of the enzymes in the CL biosynthesis and remodeling pathways in both the adult and pediatric heart. Significantly lower total and (18:2)4CL (the beneficial species) content was demonstrated in myocardium from pediatric patients with IDC compared to NF controls. Analysis of mitochondrial gene transcripts was used to demonstrate that there is no decrease in mitochondrial content. Expression of two biosynthesis enzymes and one remodeling enzyme was significantly lower in pediatric IDC compared to NF controls. Expression of two phospholipases involved in CL degradation were also altered, one up and one down-regulated. Except for one remodeling enzyme, these changes are unique from those in the failing adult heart. Conclusion Similar to what has been seen in adults and in a rat model of IDC, total and (18:2)4CL are lower in pediatric IDC. Unique CL species profiles are seen in heart tissue from children with IDC compared to adults. Differences in CL biosynthesis and remodeling enzyme expression likely explain the differences in CL profiles observed in IDC and implicate unique age-related mechanisms of disease.

Background Circulating microparticles have emerged as biomarkers and effectors of vascular disease. Elevated rates of cardiovascular disease are seen in HIV ‐1–seropositive individuals. The aims of this study were to determine: (1) if circulating microparticles are elevated in antiretroviral therapy–treated HIV ‐1–seropositive adults; and (2) the effects of microparticles isolated from antiretroviral therapy –treated HIV ‐1–seropositive adults on endothelial cell function, in vitro. Methods and Results Circulating levels of endothelial‐, platelet‐, monocyte‐, and leukocyte‐derived microparticles were determined by flow cytometry in plasma from 15 healthy and 15 antiretroviral therapy–treated, virologically suppressed HIV ‐1–seropositive men. Human umbilical vein endothelial cells were treated with microparticles from individual subjects for 24 hours; thereafter, endothelial cell inflammation, oxidative stress, senescence, and apoptosis were assessed. Circulating concentrations of endothelial‐, platelet‐, monocyte‐, and leukocyte‐derived microparticles were significantly higher (≈35%–225%) in the HIV ‐1–seropositive compared with healthy men. Microparticles from HIV ‐1–seropositive men induced significantly greater endothelial cell release of interleukin‐6 and interleukin‐8 (≈20% and ≈35%, respectively) and nuclear factor‐κB expression while suppressing anti‐inflammatory microRNAs (miR‐146a and miR‐181b). Intracellular reactive oxygen species production and expression of reactive oxygen species –related heat shock protein 70 were both higher in cells treated with microparticles from the HIV ‐1–seropositive men. In addition, the percentage of senescent cells was significantly higher and sirtuin 1 expression lower in cells treated with HIV ‐1–related microparticles. Finally, caspase‐3 was significantly elevated by microparticles from HIV ‐1–seropositive men. Conclusions Circulating concentrations of endothelial‐, platelet‐, monocyte‐, and leukocyte‐derived microparticles were higher in antiretroviral therapy–treated HIV ‐1–seropositive men and adversely affect endothelial cells promoting cellular inflammation, oxidative stress, senescence, and apoptosis. Circulating microparticles may contribute to the vascular risk associated with HIV ‐1 infection.