The mir-200 family regulates key pathogenic events in ascending aortas of individuals with bicuspid aortic valves.

Background: An individual with a bicuspid aortic valve (BAV) runs a substantially higher risk of developing aneurysm in the ascending aorta compared to the normal population with tricuspid aortic valves (TAV). Aneurysm formation in patients with BAV and TAV is known to be distinct at the molecular level but the underlying mechanisms are undefined. Here, we investigated the still incompletely described role of microRNAs (miRNAs), important post-transcriptional regulators of gene expression, in such aortic disease of patients with BAV as compared with TAV.

Loss of Vascular Myogenic Tone in miR-143/145 Knockout Mice Is Associated With Hypertension-Induced Vascular Lesions in Small Mesenteric Arteries.

Objective: Pressure-induced myogenic tone is involved in autoregulation of local blood flow and confers protection against excessive pressure levels in small arteries and capillaries. Myogenic tone is dependent on smooth muscle microRNAs (miRNAs), but the identity of these miRNAs is unclear. Furthermore, the consequences of altered myogenic tone for hypertension-induced damage to small arteries are not well understood.

Endothelial basement membrane laminin 511 is essential for shear stress response.

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Pyk2 inhibition promotes contractile differentiation in arterial smooth muscle.

Modulation from contractile to synthetic phenotype of vascular smooth muscle cells is a central process in disorders involving compromised integrity of the vascular wall. Phenotype modulation has been shown to include transition from voltage-dependent toward voltage-independent regulation of the intracellular calcium level, and inhibition of non-voltage dependent calcium influx contributes to maintenance of the contractile phenotype. One possible mediator of calcium-dependent signaling is the FAK-family non-receptor protein kinase Pyk2, which is activated by a number of stimuli in a calcium-dependent manner.

Endothelial basement membrane laminin 511 is essential for shear stress response.

Shear detection and mechanotransduction by arterial endothelium requires junctional complexes containing PECAM-1 and VE-cadherin, as well as firm anchorage to the underlying basement membrane. While considerable information is available for junctional complexes in these processes, gained largely from in vitro studies, little is known about the contribution of the endothelial basement membrane. Using resistance artery explants, we show that the integral endothelial basement membrane component, laminin 511 (laminin α5), is central to shear detection and mechanotransduction and its elimination at this site results in ablation of dilation in response to increased shear stress.

Design, synthesis and extraction studies of a new class of conformationally constrained (N,N,N',N'-tetraalkyl)7-oxabicyclo[2.2.1]heptane-2,3-dicarboxamides.

A new class of conformationally constrained 7-oxabicyclo[2.2.1]heptane-2,3-dicarboxamides (OBDA) of three secondary amines was synthesized, and their extraction behavior for trivalent and tetravalent actinides in HNO3 medium was studied.

Spontaneous activity and stretch-induced contractile differentiation are reduced in vascular smooth muscle of miR-143/145 knockout mice.

Aim: Stretch is essential for maintaining the contractile phenotype of vascular smooth muscle cells, and small non-coding microRNAs are known to be important in this process. Using a Dicer knockout model, we have previously reported that microRNAs are essential for stretch-induced differentiation and regulation of L-type calcium channel expression. The aim of this study was to investigate the importance of the smooth muscle-enriched miR-143/145 microRNA cluster for stretch-induced differentiation of the portal vein.

Mir-29 repression in bladder outlet obstruction contributes to matrix remodeling and altered stiffness.

Recent work has uncovered a role of the microRNA (miRNA) miR-29 in remodeling of the extracellular matrix. Partial bladder outlet obstruction is a prevalent condition in older men with prostate enlargement that leads to matrix synthesis in the lower urinary tract and increases bladder stiffness. Here we tested the hypothesis that miR-29 is repressed in the bladder in outlet obstruction and that this has an impact on protein synthesis and matrix remodeling leading to increased bladder stiffness.

Stretch-dependent smooth muscle differentiation in the portal vein-role of actin polymerization, calcium signaling, and microRNAs.

The mechanical forces acting on SMC in the vascular wall are known to regulate processes such as vascular remodeling and contractile differentiation. However, investigations to elucidate the underlying mechanisms of mechanotransduction in smooth muscle have been hampered by technical limitations associated with mechanical studies on pressurized small arteries, due primarily to the small amount of available tissue. The murine portal vein is a relatively large vessel showing myogenic tone that in many respects recapitulates the properties of small resistance vessels.

Expression of microRNAs is essential for arterial myogenic tone and pressure-induced activation of the PI3-kinase/Akt pathway.

Aims: The myogenic response is the intrinsic ability of small arteries to constrict in response to increased intraluminal pressure. Although microRNAs have been shown to play a role in vascular smooth muscle function, their importance in the regulation of the myogenic response is not known. In this study, we investigate the role of microRNAs in the regulation of myogenic tone by using smooth muscle-specific and tamoxifen-inducible deletion of the endonuclease Dicer in mice.

Stretch-sensitive down-regulation of the miR-144/451 cluster in vascular smooth muscle and its role in AMP-activated protein kinase signaling.

Vascular smooth muscle cells are constantly exposed to mechanical force by the blood pressure, which is thought to regulate smooth muscle growth, differentiation and contractile function. We have previously shown that the expression of microRNAs (miRNAs), small non-coding RNAs, is essential for regulation of smooth muscle phenotype including stretch-dependent contractile differentiation. In this study, we have investigated the effect of mechanical stretch on miRNA expression and the role of stretch-sensitive miRNAs for intracellular signaling in smooth muscle.