Therapeutic Antibody Against Phosphorylcholine Preserves Coronary Function and Attenuates Vascular F-FDG Uptake in Atherosclerotic Mice.

This study showed that treatment with a therapeutic monoclonal immunoglobulin-G1 antibody against phosphorylcholine on oxidized phospholipids preserves coronary flow reserve and attenuates atherosclerotic inflammation as determined by the uptake of F-fluorodeoxyglucose in atherosclerotic mice. The noninvasive imaging techniques represent translational tools to assess the efficacy of phosphorylcholine-targeted therapy on coronary artery function and atherosclerosis in clinical studies.

Clearance of cardiac troponin T with and without kidney function.

Objective: The extent of kidney-dependent clearance of the cardiac damage biomarker cardiac troponin T (cTnT) is not known.

Methods And Results: We examined clearance of cTnT after injection of heart extracts in rats with or without clamped kidney vessels. The extent of degradation of cTnT to fragments able to pass the glomerular membrane and the kidney extraction index of cTnT was examined in human subjects.

Genetic Disruption of Protein Kinase STK25 Ameliorates Metabolic Defects in a Diet-Induced Type 2 Diabetes Model.

Understanding the molecular networks controlling ectopic lipid deposition, glucose tolerance, and insulin sensitivity is essential to identifying new pharmacological approaches to treat type 2 diabetes. We recently identified serine/threonine protein kinase 25 (STK25) as a negative regulator of glucose and insulin homeostasis based on observations in myoblasts with acute depletion of STK25 and in STK25-overexpressing transgenic mice. Here, we challenged Stk25 knockout mice and wild-type littermates with a high-fat diet and showed that STK25 deficiency suppressed development of hyperglycemia and hyperinsulinemia, improved systemic glucose tolerance, reduced hepatic gluconeogenesis, and increased insulin sensitivity.

Prenatal essential fatty acid deficiency in mice results in long-term gender-specific effects on body weight and glucose metabolism.

Essential fatty acids are important for normal growth and development in early life. However, the long-term effects of prenatal essential fatty acid deficiency (EFAD) on the adult metabolism remain to be determined. The aim of this study was to investigate the effects of an EFAD diet given to mice during late gestation on body weight and body composition, and metabolism in the adult offspring.

Postnatal deficiency of essential fatty acids in mice results in resistance to diet-induced obesity and low plasma insulin during adulthood.

Our objective was to investigate the long-term metabolic effects of postnatal essential fatty acid deficiency (EFAD). Mouse dams were fed an EFAD diet or an isoenergetic control diet 4 days before delivery and throughout lactation. The pups were weaned to standard diet (STD) and were later subdivided into two groups: receiving high fat diet (HFD) or STD.

Blood pressure is the major driving force for plaque formation in aortic-constricted ApoE-/- mice.

Objective: Using an aortic constriction model in mice, we studied whether the increase in pressure or the activation of the renin-angiotensin system (RAS) and its main receptors is the main driving force for plaque progression.

Methods: Male ApoE mice underwent sham surgery or placement of a suprarenal silver clip around the aorta (AoC). Half the group was treated with the selective AT1 receptor antagonist losartan (30 mg/kg per day) for 4 weeks.

Platelet-derived growth factor B retention is essential for development of normal structure and function of conduit vessels and capillaries.

Objective: Extracellular retention of PDGF-B has been proposed to play an important role in PDGF-B signalling. We used the PDGF-B retention motif knockout mouse (RetKO) to study the effects of retention motif deletion on development of micro- and macrovascular structure and function.

Methods: Passive and active properties of conduit vessels were studied using myograph techniques and histological examination.

Short-term administration of growth hormone (GH) lowers blood pressure by activating eNOS/nitric oxide (NO)-pathway in male hypophysectomized (Hx) rats.

Background: The aim of the study was to evaluate the acute and continuous (up to 14 days of treatment) effect of growth hormone (GH) on blood pressure (BP) regulation and to investigate the interplay between GH, nitric oxide (NO) and BP. In un-supplemented and GH supplemented hypophysectomized (Hx) male rats as well as intact rats, continuous resting mean arterial blood pressure (MAP) was measured using telemetry. Baroreceptor activity and the influences of NO on BP control were assessed during telemetric measurement.

Endothelial dysfunction in growth hormone transgenic mice.

Acromegaly [overproduction of GH (growth hormone)] is associated with cardiovascular disease. Transgenic mice overexpressing bGH (bovine GH) develop hypertension and hypercholesterolaemia and could be a model for cardiovascular disease in acromegaly. The aims of the present study were to investigate the effects of excess GH on vascular function and to test whether oxidative stress affects endothelial function in bGH transgenic mice.

Angiotensin II, type 2 receptor is not involved in the angiotensin II-mediated pro-atherogenic process in ApoE-/- mice.

Objective: Angiotensin II (Ang II) accelerates atherogenesis in ApoE mice via the angiotensin II, type 1 receptor (AT1) while the type 2 receptor (AT2) is suggested to counteract atherogenesis. To confirm and further explore this possibility, we studied the effect of AT2 receptor antagonism on Ang II-accelerated atherosclerosis.

Methods: ApoE mice were fed a standard or high cholesterol diet (1.

Haemodynamically significant plaque formation and regional endothelial dysfunction in cholesterol-fed ApoE-/- mice.

Flow-mediated vasodilation is suggested as one of the mechanisms involved in arterial expansive remodelling, which is thought to be a defence mechanism in atherogenesis. In the present study, we tested the hypothesis that lumen obstructive plaque formation is associated with failure of NO (nitric oxide)-dependent vasodilation in conduit vessels. Cardiac function and aortic root flow velocities were assessed using high-resolution echocardiography and two-dimensional-guided pulsed Doppler in ApoE(-/-) (apolipoprotein E-deficient) mice fed a standard or high-cholesterol diet.

A technique to estimate the rate of whole body nitric oxide formation in conscious mice.

Objective: We have established a technique to estimate the total rate of nitric oxide (NO) formation in mice, based on inhalation of a stable oxygen isotope (18O(2)). Changes of NO production with age were also studied.

Methods: The experiments were performed in eight-week- (n=6) and eight-month-old (n=6-7), respectively, female (C57/Bl6xCBAca) mice.

Cardiovascular and renal phenotyping of genetically modified mice: a challenge for traditional physiology.

1. The advent of techniques to genetically modify experimental animals and produce directed mutations in both a conditional and tissue-specific manner has dramatically opened up new fields for physiologists in cardiovascular and renal research. 2.

GH and IGF-I regulate the expression of endothelial nitric oxide synthase (eNOS) in cardiovascular tissues of hypophysectomized female rats.

Objective: This study explored whether short-term replacement therapy with growth hormone (GH) affects blood pressure (BP), heart rate (HR) and endothelial nitric oxide synthase (eNOS) expression in cardiovascular tissues in hypophysectomized (Hx) female rats.

Design And Methods: BP, HR and the expression of eNOS in the aorta, caval vein and heart were studied in Hx female rats and in Hx female rats that underwent 7 days treatment with GH and thyroxine+glucocorticoids ([T(4)+GC]). Insulin-like growth factor-I (IGF-I) was included in a second experimental protocol to explore the indirect effect of GH.

Brief losartan treatment in young spontaneously hypertensive rats abates long-term blood pressure elevation by effects on renal vascular structure.

Objective: We studied the importance of regional vascular structural changes for the long-term antihypertensive effect of brief angiotensin II receptor blockade with losartan in young spontaneously hypertensive rats (SHRs).

Design/methods: SHRs were treated from 3 to 8 weeks of age with losartan (SHRLos, 30 mg/kg per day in drinking water) or vehicle (SHRCon). Mean arterial blood pressure (MAP) was measured using a telemetric technique from 12 to 25 weeks of age.