Proprotein convertase subtilisin kexin type 9 (PCSK9) is an important regulator of hepatic low-density lipoprotein (LDL)-cholesterol levels. We have previously shown that PCSK9 is expressed in cultured smooth muscle cells (SMCs) and it is detectable in human carotid atherosclerotic plaques. The aim of the present study was to compare the vascular changes induced by periadventitial placement of a non-occlusive constrictive silicone collar for 9 weeks around the common carotid artery of WT and PCSK9 deficient mice. Collared carotids of the PCSK9-/- mice (n=6 per group) showed a less marked intimal thickening compared WT mice (19055±10158 μm2 vs. 34989±12823 μm2; *P0.05) , a decreased intimal media ratio (2.54±1.67 vs. 0.82±0.70 *P<0.05) and higher lumen area (11821±7980 μm2 vs. 18830±8816 μm2). Carotid lesions of WT mice had an elevated content of SMCs (21.0±7.56% vs. 10.7±1.97% P<0.05) and collagen (18.38±7.90% vs. 10.45±9.11%; **P<0.01) and no difference in macrophage content was detected between the two groups. Cultured SMCs isolated from WT mice showed lower levels of the contractile markers smooth muscle α-actin (-94±6%; ***P<0.001 ) and calponin (-74±18%; ***P<0.001 ), and increased Col1a1 mRNA levels (2.30±0.3 fold ***P<0.001) after stimulation with PDGF-BB. Finally, the proliferation rate of PCSK9-/- SMCs was significantly lower compared to PCSK9-/- SMCs reconstituted with PCSK9 encoding plasmid (doubling time 41.2±1.9 h vs. 32.2±3.1 h; ***P=0.01). Taken together, the present results suggest a favorable action of PCSK9 on neointima formation in response to perivascular carotid, probably facilitating the phenotypic switch of medial SMCs and their proliferation.
|Titolo:||PCSK9 deficient mice are protected from neointima formation in carotid artery injury model|
|Data di pubblicazione:||10-set-2013|
|Parole Chiave:||pcsk9 ; smooth muscle cells ; atherosclerosis|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Enti collegati al convegno:||European Lipoprotein Club|
|Citazione:||PCSK9 deficient mice are protected from neointima formation in carotid artery injury model / N. Ferri, G. Tibolla, R. Baetta, P. Costet, A. Corsini, A.L. Catapano. ((Intervento presentato al 36. convegno European Lipoprotein Club meeting tenutosi a Tutzing nel 2013.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|