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Low levels of low-density lipoprotein-C associated with proprotein convertase subtilisin kexin 9 inhibition do not increase the risk of hemorrhagic transformation.
Tran-Dinh, Alexy; Levoye, Angélique; Lambert, Gilles; Louedec, Liliane; Journé, Clément; Meilhac, Olivier; Amarenco, Pierre.
Afiliação
  • Tran-Dinh A; From the Inserm UMR1148, Paris7 University, Xavier Bichat Hospital, Paris, France (A.T.-D., A.L., L.L., C.J., O.M., P.A.); Paris 7 University, Université Paris Diderot, Paris, France (A.T.-D., P.A.); CHU Bichat Stroke Center, Paris, France (P.A.); CHU de La Réunion, Saint-Pierre, France (O.M.); Pari
  • Levoye A; From the Inserm UMR1148, Paris7 University, Xavier Bichat Hospital, Paris, France (A.T.-D., A.L., L.L., C.J., O.M., P.A.); Paris 7 University, Université Paris Diderot, Paris, France (A.T.-D., P.A.); CHU Bichat Stroke Center, Paris, France (P.A.); CHU de La Réunion, Saint-Pierre, France (O.M.); Pari
  • Lambert G; From the Inserm UMR1148, Paris7 University, Xavier Bichat Hospital, Paris, France (A.T.-D., A.L., L.L., C.J., O.M., P.A.); Paris 7 University, Université Paris Diderot, Paris, France (A.T.-D., P.A.); CHU Bichat Stroke Center, Paris, France (P.A.); CHU de La Réunion, Saint-Pierre, France (O.M.); Pari
  • Louedec L; From the Inserm UMR1148, Paris7 University, Xavier Bichat Hospital, Paris, France (A.T.-D., A.L., L.L., C.J., O.M., P.A.); Paris 7 University, Université Paris Diderot, Paris, France (A.T.-D., P.A.); CHU Bichat Stroke Center, Paris, France (P.A.); CHU de La Réunion, Saint-Pierre, France (O.M.); Pari
  • Journé C; From the Inserm UMR1148, Paris7 University, Xavier Bichat Hospital, Paris, France (A.T.-D., A.L., L.L., C.J., O.M., P.A.); Paris 7 University, Université Paris Diderot, Paris, France (A.T.-D., P.A.); CHU Bichat Stroke Center, Paris, France (P.A.); CHU de La Réunion, Saint-Pierre, France (O.M.); Pari
  • Meilhac O; From the Inserm UMR1148, Paris7 University, Xavier Bichat Hospital, Paris, France (A.T.-D., A.L., L.L., C.J., O.M., P.A.); Paris 7 University, Université Paris Diderot, Paris, France (A.T.-D., P.A.); CHU Bichat Stroke Center, Paris, France (P.A.); CHU de La Réunion, Saint-Pierre, France (O.M.); Pari
  • Amarenco P; From the Inserm UMR1148, Paris7 University, Xavier Bichat Hospital, Paris, France (A.T.-D., A.L., L.L., C.J., O.M., P.A.); Paris 7 University, Université Paris Diderot, Paris, France (A.T.-D., P.A.); CHU Bichat Stroke Center, Paris, France (P.A.); CHU de La Réunion, Saint-Pierre, France (O.M.); Pari
Stroke ; 45(10): 3086-8, 2014 Oct.
Article em En | MEDLINE | ID: mdl-25123222
ABSTRACT
BACKGROUND AND

PURPOSE:

Low levels of low-density lipoprotein-cholesterol (LDL-C) are suspected to be associated with a risk of hemorrhagic transformation after ischemic stroke. We assessed the risk of hemorrhagic transformation after cerebral ischemia/reperfusion in mice with low levels of LDL-C resulting from proprotein convertase subtilisin kexin 9 (PCSK9) deficiency.

METHODS:

PCSK9-/- and PCSK9+/+ mice were fed with a high-fat/high-cholesterol (21%/0.15%) diet for 1 month. Plasma lipids were measured using colorimetric assays. PCSK9-/- and PCSK9+/+ mice (n=15 per group) were subjected to a 4-hour intraluminal occlusion of the middle cerebral artery followed by 20 hours of reperfusion. Spontaneous hemorrhagic transformation was assessed by quantification of hemoglobin in ischemic tissue. In vitro, a cell model of blood-brain barrier was used to test endothelial barrier integrity in response to decreasing concentrations of LDL-C from 1 to 0.25g/L in ischemia/reperfusion conditions.

RESULTS:

PCSK9-/- mice had lower LDL-C, high-density lipoprotein-cholesterol, and total cholesterol levels than PCSK9+/+ mice before and after 1 month on the high-fat/high-cholesterol diet. Hemoglobin concentration in ischemic cerebral tissue was not different between PCSK9-/- and PCSK9+/+ mice (31.5 [18.9-60.1] and 32.8 [14.7-69.9] ng/mg protein, respectively; P=0.81). Infarct volume was also similar in both groups (P=0.66). Incubation of human cerebral endothelial cells with decreasing concentrations of LDL-C under ischemia/reperfusion conditions did not alter blood-brain barrier permeability.

CONCLUSIONS:

Low levels of LDL-C did not increase the risk of hemorrhagic transformation after cerebral ischemia/reperfusion in mice. Our observations suggest that PCSK9 inhibition, leading to LDL-C lowering, should not increase hemorrhagic complications after acute ischemic stroke.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Hemorragia Cerebral / Acidente Vascular Cerebral / Pró-Proteína Convertases / LDL-Colesterol Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Animals / Humans / Male Idioma: En Revista: Stroke Ano de publicação: 2014 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Hemorragia Cerebral / Acidente Vascular Cerebral / Pró-Proteína Convertases / LDL-Colesterol Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Animals / Humans / Male Idioma: En Revista: Stroke Ano de publicação: 2014 Tipo de documento: Article