ABSTRACT
In China, automated blood pressure monitors have been readily available for home use. Home blood pressure monitoring has been indispensable in the management of hypertension. There is therefore a need to establish guidelines for home blood pressure monitoring on the basis of the 2012 consensus document. In this guidelines document, the committee put forward recommendations on the selection and calibration of blood pressure measuring devices, the frequency (times) and duration (days) of blood pressure measurement, and the diagnostic threshold of home blood pressure.
Subject(s)
Blood Pressure Monitoring, Ambulatory , Hypertension , Blood Pressure , Blood Pressure Determination , China/epidemiology , Humans , Hypertension/diagnosis , SphygmomanometersABSTRACT
Endothelial progenitor cell (EPC) dysfunction is a key contributor to diabetic refractory wounds. Endothelial nitric oxide synthase (eNOS), which critically regulates the mobilization and function of EPCs, is uncoupled in diabetes due to decreased cofactor tetrahydrobiopterin (BH4). We tested whether GTP cyclohydrolase I (GTPCH I), the rate-limiting enzyme of BH4 synthesis, preserves EPC function in type 1 diabetic mice. Type 1 diabetes was induced in wild-type (WT) and GTPCH I transgenic (Tg-GCH) mice by intraperitoneal injection of streptozotocin (STZ). EPCs were isolated from the peripheral blood and bone marrow of WT, Tg-GCH, and GTPCH I-deficient hph-1 mice. The number of EPCs was significantly lower in STZ-WT mice and hph-1 mice and was rescued in STZ Tg-GCH mice. Furthermore, GTPCH I overexpression improved impaired diabetic EPC migration and tube formation. EPCs from WT, Tg-GCH, and STZ-Tg-GCH mice were administered to diabetic excisional wounds and accelerated wound healing significantly, with a concomitant augmentation of angiogenesis. Flow cytometry measurements showed that intracellular nitric oxide (NO) levels were reduced significantly in STZ-WT and hph-1 mice, paralleled by increased superoxide anion levels; both were rescued in STZ-Tg-GCH mice. Western blot analysis revealed that thrombospondin-1 (TSP-1) was significantly upregulated in the EPCs of STZ-WT mice and hph-1 mice and suppressed in STZ-treated Tg-GCH mice. Our results demonstrate that the GTPCH I/BH4 pathway is critical to preserve EPC quantity, function, and regenerative capacity during wound healing in type 1 diabetic mice at least partly through the attenuation of superoxide and TSP-1 levels and augmentation of NO level.
Subject(s)
Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Type 1/pathology , Endothelial Cells/drug effects , GTP Cyclohydrolase/physiology , Hematopoietic Stem Cells/drug effects , Oxidative Stress/genetics , Thrombospondin 1/metabolism , Wound Healing/genetics , Animals , Biopterins/analogs & derivatives , Biopterins/metabolism , Cell Proliferation , Down-Regulation/genetics , Endothelial Cells/pathology , Endothelial Cells/physiology , GTP Cyclohydrolase/genetics , Hematopoietic Stem Cells/pathology , Hematopoietic Stem Cells/physiology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Wound Healing/drug effectsABSTRACT
Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase (NOS). In the cardiovascular system, endothelial NOS (eNOS) has a major role in maintaining vascular tone and endothelial function, as well as in mediating many other vascular protective properties. Evidence from humans and animals have demonstrated that decreased BH4 bioavailability, with subsequent uncoupling of eNOS, has significant effects on the pathogenesis of endothelial dysfunction, which is a hallmark of vascular injury in cardiovascular disorders, including hypertension, hyperlipidemia, and diabetes. In this review, we discuss the synthesis of BH4, its molecular mechanisms regulating eNOS coupling, the pathophysiologic roles of decreased BH4 bioavailability in cardiovascular diseases, and the potential therapeutic application of BH4 in clinics.
Subject(s)
Biopterins/analogs & derivatives , Nitric Oxide Synthase Type III/metabolism , Animals , Biopterins/metabolism , Cardiovascular Diseases/enzymology , Cardiovascular Diseases/metabolism , Humans , Oxidation-ReductionABSTRACT
OBJECTIVE: To investigate the relationship between the expression of neuronal acetylcholine receptor alpha 7 (nAChRalpha7) and the role of nAChRalpha7 in the development of asthma by detecting the expression of nAChR alpha7 on CD(4)(+) T lymphocytes in the peripheral blood and the level of cytokines IFN-gamma and IL-4 in the blood serum from children with asthma. METHODS: Thirty patients in the asthma group and 20 healthy children in the normal control group were included. Peripheral blood was collected, and the serum was harvested. The expression of nAChRalpha7 on CD(3)(+) and CD(4)(+) cells were detected by flow cytometry. The levels of IFN-gamma and IL-4 in the serum were detected by ELISA. RESULTS: The expression of nAChRalpha7 on CD(4)(+) T lymphocytes from children with asthma was higher than that from normal controls (t = 2.53, P < 0.05). Compared with the control group, the level of IL-4 in the serum of the asthma group was higher (t = 5.42, P < 0.01) but the level of IFN-gamma was lower (t = 4.11, P < 0.01). There were positive correlation between nAChRalpha7 and IL-4 (r = 0.688, P < 0.01) and negative correlation between nAChRalpha7 and IFN-gamma (r = -0.476, P < 0.01). CONCLUSION: nAChRalpha7 was shown to influence the balance of Th1/Th2 and it may play an important role in the development of asthma.
