Choosing Wisely - An international and multimorbid perspective.

Some medical diagnostic and therapeutic interventions are non-beneficial or even harmful. The Choosing Wisely campaign has encouraged the generation of "top five" lists of unnecessary low-value services in different specialist areas. In the USA alone, where the campaign was launched, these lists include a total of 450 evidence-based recommendations.

Endothelial Rictor is crucial for midgestational development and sustained and extensive FGF2-induced neovascularization in the adult.

To explore the general requirement of endothelial mTORC2 during embryonic and adolescent development, we knocked out the essential mTORC2 component Rictor in the mouse endothelium in the embryo, during adolescence and in endothelial cells in vitro. During embryonic development, Rictor knockout resulted in growth retardation and lethality around embryonic day 12. We detected reduced peripheral vascularization and delayed ossification of developing fingers, toes and vertebrae during this confined midgestational period.

Hypoxia potentiates tumor necrosis factor-α induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in white and brown adipocytes.

Obesity involves hypoxic adipose tissue and low-grade chronic inflammation. We investigated the impact of hypoxia on inflammatory response to TNF-α in white and brown adipocytes. In response to TNF-α, the expression of the inducible enzymes iNOS and COX-2 was prominently and selectively potentiated during hypoxia while only moderately under normoxia.

Rictor in perivascular adipose tissue controls vascular function by regulating inflammatory molecule expression.

Objective: Perivascular adipose tissue (PVAT) wraps blood vessels and modulates vasoreactivity by secretion of vasoactive molecules. Mammalian target of rapamycin complex 2 (mTORC2) has been shown to control inflammation and is expressed in adipose tissue. In this study, we investigated whether adipose-specific deletion of rictor and thereby inactivation of mTORC2 in PVAT may modulate vascular function by increasing inflammation in PVAT.

Nuclear PIM1 confers resistance to rapamycin-impaired endothelial proliferation.

The PIM serine/threonine kinases and the mTOR/AKT pathway integrate growth factor signaling and promote cell proliferation and survival. They both share phosphorylation targets and have overlapping functions, which can partially substitute for each other. In cancer cells PIM kinases have been reported to produce resistance to mTOR inhibition by rapamycin.

B2-kinin receptor plays a key role in B1-, angiotensin converting enzyme inhibitor-, and vascular endothelial growth factor-stimulated in vitro angiogenesis in the hypoxic mouse heart.

Aims: Angiotensin converting enzyme (ACE) inhibition reduces heart disease and vascular stiffness in hypertension and leads to kinin accumulation. In this study, we analysed the role and importance of two kinin receptor subtypes in angiogenesis during ACE inhibition in an in vitro model of angiogenesis of the mouse heart.

Methods And Results: First, we analysed the angiogenic properties of bradykinin and enalapril on wild-type C57Bl/6 and B2 receptor(-/-) mouse heart under normoxia (21% O(2)) and hypoxia (1% O(2)) in vitro and the contribution of B1 and B2 kinin receptors to this effect.

Angiotensin II induces angiogenesis in the hypoxic adult mouse heart in vitro through an AT2-B2 receptor pathway.

Angiotensin II is a vasoactive peptide that may affect vascularization of the ischemic heart via angiogenesis. In this study we aimed at studying the mechanisms underlying the angiogenic effects of angiotensin II under hypoxia in the mouse heart in vitro. Endothelial sprout formation from pieces of mouse hearts was assessed under normoxia (21% O(2)) and hypoxia (1% O(2)) during a 7-day period of in vitro culture.

Effects of anti-hypertensive drugs on vessel rarefaction.

The microcirculation largely determines peripheral vascular resistance and substantially contributes to arterial hypertension. In both human arterial hypertension and animal models of hypertension, genetic, fetal and other mechanisms associated with hypertension can reduce the formation and number of microvessels (i.e.

Formation of new blood vessels in the heart can be studied in cell cultures.

Controlled induction of the formation of new microvessels, i.e., therapeutic angiogenesis, may be used one day to treat patients that for example had suffered a myocardial infarction.

Hypoxia-induced endothelial proliferation requires both mTORC1 and mTORC2.

A central regulator of cell growth that has been implicated in responses to stress such as hypoxia is mTOR (mammalian Target Of Rapamycin). We have shown previously that mTOR is required for angiogenesis in vitro and endothelial cell proliferation in response to hypoxia. Here we have investigated mTOR-associated signaling components under hypoxia and their effects on cell proliferation in rat aortic endothelial cells (RAECs).

Moderate-to-severe blood pressure elevation at ED entry: hypertension or normotension?

Purpose: It is controversial whether arterial hypertension (AHT) can be diagnosed in the emergency department (ED). We sought to prospectively investigate the natural time course of blood pressure (BP) to define an optimal period for AHT screening in ED patients with an elevated initial BP.

Procedures: Patients with a BP greater than 160/100 mm Hg upon ED admission underwent repeated BP measurements every 5 minutes for 2 hours using an automated device.

A versatile in vitro assay for investigating angiogenesis of the heart.

Neovascularization in the heart is usually investigated with models of angiogenesis in vivo. Here we present a simple model that allows investigating heart angiogenesis in mice and rats in vitro. Small pieces of left ventricular myocardium were cultured in three-dimensional fibrin gels for 10 days.

Hypoxia enhances vascular cell proliferation and angiogenesis in vitro via rapamycin (mTOR)-dependent signaling.

Angiogenesis and vascular cell proliferation are pivotal in physiological and pathological processes including atherogenesis, restenosis, wound healing, and cancer development. Here we show that mammalian target of rapamycin (mTOR) signaling plays a key role in hypoxia-triggered smooth muscle and endothelial proliferation and angiogenesis in vitro. Hypoxia significantly increased DNA synthesis and proliferative responses to platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) in rat and human smooth muscle and endothelial cells.

Inhibition of NO biosynthesis, but not elevated blood pressure, reduces angiogenesis in rat models of secondary hypertension.

Arterial hypertension (AH) is characterized by reduced nitric oxide (NO) biosynthesis, vasoconstriction, and reduced microvascular density. In this study we asked whether AH also reduces the number of microvessels by impairing angiogenesis. AH was induced in Dahl salt-sensitive rats (DSS) with a salt diet and in Wistar-Kyoto rats by inhibiting NO formation with Nomega-nitro-L-arginine (NNA).