Renal Nerve-Mediated Erythropoietin Release Confers Cardioprotection During Remote Ischemic Preconditioning.

Background: Remote ischemic preconditioning (RIPC) induced by transient limb ischemia is a powerful innate mechanism of cardioprotection against ischemia. Several described mechanisms explain how RIPC may act through neural pathways or humoral factors; however, the mechanistic pathway linking the remote organ to the heart has not yet been fully elucidated. This study aimed to investigate the mechanisms underlying the RIPC-induced production of Janus kinase (JAK)-signal transducer and activator of the transcription (STAT)-activating cytokines and cardioprotection by using mouse and human models of RIPC.

Involvement of iron-evoked oxidative stress in smoking-related endothelial dysfunction in healthy young men.

Background: Oxidative stress and smoking contribute to endothelial dysfunction. Iron might also play a role in oxidative stress generation and endothelial dysfunction. However, the involvement of iron in smoking-induced endothelial dysfunction in healthy smokers remains unclear.

Endothelial function in subjects with isolated low HDL cholesterol: role of nitric oxide and circulating progenitor cells.

Epidemiologic studies have shown that a low level of high-density lipoprotein (HDL) cholesterol is a risk factor for cardiovascular diseases. The purpose of this study was to determine the contribution of isolated low HDL cholesterol to endothelial function. Thirty-nine subjects with low HDL cholesterol who had no other cardiovascular risk factors were selected from the 5,417 participants from our population.

Flow-mediated vasodilation as a diagnostic modality for vascular failure.

Vascular endothelial dysfunction represents an initial step of "vascular failure," which we have recently proposed as a comprehensive syndrome of failed vascular functions that extends from risk factors to established atherosclerotic disease. The early detection of vascular failure is essential in order to appropriately intervene and prevent its progression. Many efforts have been made to assess vascular endothelial function, and one of the most promising methods is the measurement of endothelium-dependent flow-mediated vasodilation (FMD) using high-frequency ultrasonographic imaging and transient occlusion of the brachial artery.

Involvement of asymmetric dimethylarginine (ADMA) in tubulointerstitial ischaemia in the early phase of diabetic nephropathy.

Background: Decreased peritubular capillary (PTC) flow due to impaired endothelial function elicits tubulointerstitial ischaemia, thereby enhancing renal damage in chronic kidney disease, including diabetic nephropathy. Since nitric oxide (NO) is a vasodilator and known to play an important role in the maintenance of PTC flow, it is conceivable that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, may cause tubulointerstitial ischaemia, thus being involved in the progression of diabetic nephropathy. In this study, we investigated whether overexpression of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that degrades ADMA, could improve tubulointerstitial ischaemia in streptozotocin (STZ)-induced diabetic rats.

Plasma level of asymmetric dimethylarginine (ADMA) as a predictor of carotid intima-media thickness progression: six-year prospective study using carotid ultrasonography.

This study was designed to determine the relationship between plasma asymmetric dimethylarginine (ADMA) and the development of carotid atherosclerosis. Cross-sectional studies have revealed that plasma ADMA concentration is correlated with the intima-media thickness (IMT) of the carotid artery, but no prospective studies have appeared. Therefore we prospectively investigated whether or not plasma ADMA level can predict IMT progression.

Dimethylarginine dimethylaminohydrolase prevents progression of renal dysfunction by inhibiting loss of peritubular capillaries and tubulointerstitial fibrosis in a rat model of chronic kidney disease.

Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, is mainly degraded by dimethylarginine dimethylaminohydrolase (DDAH). It was recently reported that reduced DDAH expression could contribute to ADMA accumulation and subsequent elevation of BP in an experimental model of chronic kidney disease (CKD). ADMA is a strong predictor of the progression of CKD as well.

Fluvastatin alters platelet aggregability in patients with hypercholesterolemia: possible improvement of intraplatelet redox imbalance via HMG-CoA reductase.

Background: Hypercholesterolemia enhances platelet aggregability. Statins have beneficial effects on cardiovascular events. The purpose of this study is to investigate whether statins inhibit platelet aggregation and, if so, the mechanisms.

Elevated circulating oxidized LDL levels in Japanese subjects with the metabolic syndrome.

In the present study, we examined the relationship between circulating oxidized low-density lipoprotein (LDL) and the metabolic syndrome in Japanese patients. Subjects who had no histories of coronary or peripheral artery disease and were taking no medications (n=119; age 57+/-10 years; male/female, 90:29) underwent a complete history and physical examination, determination of blood chemistries and oxidized LDL levels. In stepwise regression analysis, triglycerides (p=0.

Molecular mechanism for elevation of asymmetric dimethylarginine and its role for hypertension in chronic kidney disease.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. ADMA is generated by protein methyltransferase (PRMT) and is metabolized mainly by dimethylarginine dimethylaminohydrolase (DDAH). ADMA levels are reported to increase in patients with chronic kidney disease (CKD), thereby playing a role in the pathogenesis of accelerated atherosclerosis in this population.

Plasma levels of asymmetric dimethylarginine (ADMA) are related to intima-media thickness of the carotid artery: an epidemiological study.

Asymmetric dimethylarginine (ADMA) is a circulating endogenous nitric oxide (NO) synthase inhibitor. It has been reported that plasma levels of ADMA are related to intima-media thickness (IMT) in small numbers. We investigated this issue in a large number of subjects without overt cerebro-cardiovascular diseases.

[Calcium antagonists and ischemic heart disease].

Long-acting calcium antagonists, which have a wide-variety of anti-atherogenic properties, are well-tolerable and highly efficacious blood pressure lowering agents. Since a number of large prospective trials demonstrated the improvement of clinical outcomes in patients with coronary artery diseases, long-acting calcium antagonists may play a central role in the therapeutic strategy for ischemic heart disease.

Polymorphonuclear leukocytes may impair endothelial function: results of crossover randomized study of lipid-lowering therapies.

Objectives: To examine whether polymorphonuclear leukocytes (PMNs) in hypercholesterolemia (HC) are activated to generate large amount of superoxide in vivo and hence impair endothelial function and, if so, whether statins, which possess anti-inflammatory properties, may restore PMN-mediated endothelial dysfunction.

Methods And Results: At baseline, subjects with HC showed impaired endothelial function (P<0.001), estimated by flow-mediated vasodilation of the brachial artery, and increased susceptibility of low-density lipoprotein (LDL) to oxidation (P<0.

Regulation of cytokine-induced nitric oxide synthesis by asymmetric dimethylarginine: role of dimethylarginine dimethylaminohydrolase.

In response to vascular insults, inflammatory cytokines stimulate vascular smooth muscle cells (SMCs) to express an inducible isoform of nitric oxide synthase (iNOS). Asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor, is metabolized by dimethylarginine dimethylaminohydrolase (DDAH). To determine whether the ADMA-DDAH system regulates cytokine-induced NO production, cultured rat SMCs were exposed to interleukin-1beta (IL-1beta).

Plasma homocysteine levels and atherosclerosis in Japan: epidemiological study by use of carotid ultrasonography.

Background And Purpose: We examined whether hyperhomocysteinemia is an independent risk factor for increased carotid artery intimal-medial wall thickness (IMT) in a large, randomly selected community in Japan where the dietary habit is different and the incidence of coronary artery disease is lower compared with those of western countries.

Methods: In 1111 cases (452 men, 659 women) aged 63+/-10 years old (range, 40 to 94 years) recruited from a population-based survey performed in 1999, we measured fasting plasma total homocysteine levels and performed bilateral carotid B-mode ultrasound. The participants underwent measurements of other blood chemistries (total cholesterol, HDL cholesterol, glycosylated hemoglobin A(1c), and creatinine).