Background-Essential hypertension has been recognized as a disease resulting from a combination of environmental and genetic factors. Recent studies demonstrated that microRNAs (miRNAs) are involved in cardiac hypertrophy and heart failure. However, little is known about the roles of miRNAs in essential hypertension. Methods and Results-Using microarray-based miRNA expression profiling, we compared the miRNA expressions in plasma samples from 13 hypertensive patients and 5 healthy control subjects. Twenty-seven miRNAs were found to be differentially expressed. The expressions of selected miRNAs (miR-296 -5p, let-7e, and a human cytomegalovirus [HCMV]-encoded miRNA, hcmv-miR-UL112) were validated independently in plasma samples from 24 hypertensive patients and 22 control subjects. The absolute expression levels of hcmv-miR-UL112, miR-296 -5p, and let-7e were further determined in 127 patients and 67 control subjects (fold changes are 2.5, 0.5, and 1.7 respectively; all PϽ0.0001). Additionally, we demonstrated that interferon regulatory factor 1 is a direct target of hcmv-miR-UL112.Increased HCMV seropositivity and quantitative titers were found in the hypertension group compared with the control group (52.7% versus 30.9%, Pϭ0.0005; 1870 versus 54 copies per 1 mL plasma, PϽ0.0001). Seropositivity, log-transformed copies of HCMV, and hcmv-miR-UL112 were independently associated with an increased risk of hypertension (odds ratio, 2.48; 95% confidence interval, 1.48 to 4.15; Pϭ0.0005; odds ratio, 1.97; 95% confidence interval, 1.58 to 2.46; PϽ0.0001; and odds ratio, 2.55; 95% confidence interval, 1.98 to 3.27; PϽ0.0001, respectively). Conclusions-We report for the first time a circulating miRNA profile for hypertensive patients and demonstrate a novel link between HCMV infection and essential hypertension. These findings may reveal important insights into the pathogenesis of essential hypertension. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00420784. Key Words: cytomegalovirus Ⅲ hypertension Ⅲ interferon regulatory factor-1 Ⅲ microRNAs E ssential hypertension is a predisposing risk factor for stroke, myocardial infarction, congestive heart failure, and arterial aneurysm; it is also the leading cause of chronic renal failure. 1 Approximately 90% to 95% of hypertension, affecting Ͼ1 billion adults worldwide, is the essential hypertension subtype. 2 Discernment between essential and secondary hypertension is critical because the former has no precise cause and the latter has a clear cause usually remediable by a Clinical Perspective on p 184 microRNAs (miRNAs) are short, endogenous, noncoding RNAs that regulate gene expression at the posttranscriptional level by binding to the 3Ј untranslated regions (UTRs) of their target mRNAs. 7 Although dysregulation of miRNA expression is a feature of malignancies, 8 -10 research into miRNAs in biological processes reveals their regulation of immune cell development, 11 involvement in inflammatory response, 12 and critical participation...

Objective Hyperlipidemia-induced endothelial cell (EC) activation is considered as an initial event responsible for monocyte recruitment in atherogenesis. However, it remains poorly defined what is the mechanism underlying hyperlipidemia-induced EC activation. Here we tested a novel hypothesis that mitochondrial reactive oxygen species (mtROS) serve as signaling mediators for EC activation in early atherosclerosis. Approach and Results Metabolomics and transcriptomics analyses revealed that several lysophosphatidylcholine (LPC) species, such as 16:0, 18:0 and 18:1, and their processing enzymes, including Pla2g7 and Pla2g4c, were significantly induced in the aortas of apolipoprotein E knockout (ApoE−/−) mice during early atherosclerosis. Using electron spin resonance and flow cytometry, we found that LPC 16:0, 18:0 and 18:1 induced mtROS in primary human aortic ECs (HAECs), independently of the activities of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Mechanistically, using confocal microscopy and Seahorse XF mitochondrial analyzer, we showed that LPC induced mtROS via unique calcium entry-mediated increase of proton leak and mitochondrial O2 reduction. In addition, we found that mtROS contributed to LPC-induced EC activation by regulating nuclear binding of AP-1 and inducing intercellular adhesion molecule 1 (ICAM-1) gene expression in vitro. Furthermore, we showed that mtROS inhibitor MitoTEMPO suppressed EC activation and aortic monocyte recruitment in ApoE−/− mice using intravital microscopy and flow cytometry methods. Conclusions ATP synthesis-uncoupled, but proton leak-coupled mtROS increase mediates LPC-induced EC activation during early atherosclerosis. These results indicate that mitochondrial antioxidants are promising therapies for vascular inflammation and cardiovascular diseases.

Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefits health and prevents disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how physical activity mitigates disease.

Mitochondria are known to generate approximately 90% of cellular reactive oxygen species (ROS). The imbalance between mitochondrial reactive oxygen species (mtROS) production and removal due to overproduction of ROS and/or decreased antioxidants defense activity results in oxidative stress (OS), which leads to oxidative damage that affects several cellular components such as lipids, DNA, and proteins. Since the kidney is a highly energetic organ, it is more vulnerable to damage caused by OS and thus its contribution to the development and progression of chronic kidney disease (CKD). This article aims to review the contribution of mtROS and OS to CKD progression and kidney function deterioration.

IL-35 is induced during atherosclerosis development and inhibits mitochondrial reactive oxygen species-H3K14 acetylation-AP-1-mediated EC activation.

Based on a study of competitive substituent effects in a Claisen-Schmidt reaction, interfacial effects have been shown to play an important role in accelerated reactions that occur in thin films and droplets. A role for the interface in an accelerated C-C bond-formation reaction between 6hydroxy-1-indanone and aromatic aldehydes is indicated by cooperative interactions between p-methylbenzaldehyde and p-nitrobenzaldehyde. Additional acceleration over that occurring in bulk reactions is seen for p-methylbenzaldehyde, but only in the presence of p-nitrobenzaldehyde. A decrease in the degree of acceleration is detected when the reaction is forced electrostatically to occur inside the thin film, and the interface is shown to participate in the accelerated reactions. This experimental evidence for interfacial thin film and droplet acceleration supports a recent model and builds on earlier work which locates molecules within evaporating droplets in electrosprays.

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There are limitations in the current classification of danger associated molecular patterns (DAMP) receptors. To overcome these limitations, we propose a new paradigm by using endogenous metabolites lysophospholipids (LPLs) as a prototype. By utilizing a data mining method we pioneered, we made the following findings: 1) Endogenous metabolites such as LPLs at basal level have physiological functions; 2) under sterile inflammation, expression of some LPLs are elevated. These LPLs act as conditional DAMPs or anti-inflammatory homeostasis-associated molecular pattern molecules (HAMPs) for regulating the progression of inflammation or inhibition of inflammation, respectively; 3) receptors for conditional DAMPs and HAMPs are differentially expressed in human and mouse tissues; and 4) complex signaling mechanism exists between pro-inflammatory mediators and classical DAMPs that regulate the expression of conditional DAMPs and HAMPs. This novel insight will facilitate identification of novel conditional DAMPs and HAMPs, thus promote development of new therapeutic targets to treat inflammatory disorders.