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Pathol Biol (Paris). 2012 Feb;60(1):34-40. doi: 10.1016/j.patbio.2011.11.005. Epub 2011 Dec 26.

Protocadherin-12 deficiency leads to modifications in the structure and function of arteries in mice.

Author information

1
Inserm U882, laboratoire physiopathologie vasculaire : interactions cellulaires, signalisation et vieillissement, université Joseph-Fourier, CEA, 38054 Grenoble, France.

Abstract

We studied the role of protocadherin-12 on arterial function. This protein belongs to the cadherin superfamily and is located at the intercellular junctions of endothelial cells where it promotes homotypic cellular adhesion. We previously showed that mice deficient for PCDH12 exhibited developmental growth retardation owing to placenta defects without altering neither survival nor fertility. Here, we investigated the effects of PCDH12 deficiency on the structural, mechanical properties and functionality of arteries from adult mice. Histological studies of the PCDH12(-/-) mouse arteries have shown age-independent modifications such as ramifications of medial elastic lamellae, accompanied by the appearance of radial fibers linking together two successive concentric elastic lamellae. Mechanical studies also revealed some age-independent modifications in the PCDH12(-/-) mice arteries such as an increase in inner-diameter and circumferential mid-wall stress. Moreover, the PCDH12(-/-) mice exhibited a mild reduction of blood pressure, thus maintaining the inner-diameter close to its normal value and a normal circumferential wall stress for vascular cells. This is likely a compensation mechanism enabling normal blood flow in the arteries. The vascular phenotypic differences observed between PCDH12(-/-) and wild type mice arteries did not seem to be age-dependent, except for some results regarding the carotid artery: the reactivity to acetylcholine and the circumferential mid-wall stress decreased with ageing in the PCDH12(-/-) mice, as opposed to the increase observed in the wild types. In conclusion, deficiency in one specific interendothelial junction component leads to significant changes in the structure and function of the vascular wall. Possible explanations for the observed modifications are discussed.

PMID:
22205043
DOI:
10.1016/j.patbio.2011.11.005
[Indexed for MEDLINE]

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