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Liquid Biopsy of Extracellular Microvesicles Maps Coronary Calcification and Atherosclerotic Plaque in Asymptomatic Patients With Familial Hypercholesterolemia.
Chiva-Blanch, Gemma; Padró, Teresa; Alonso, Rodrigo; Crespo, Javier; Perez de Isla, Leopoldo; Mata, Pedro; Badimon, Lina.
Afiliación
  • Chiva-Blanch G; From the Cardiovascular Science Institute - ICCC; IIB-Sant Pau, Hospital de Sant Pau, Barcelona, Spain (G.C.-B., T.P., J.C., L.B.).
  • Padró T; From the Cardiovascular Science Institute - ICCC; IIB-Sant Pau, Hospital de Sant Pau, Barcelona, Spain (G.C.-B., T.P., J.C., L.B.).
  • Alonso R; CiberCV, Institute Carlos III, Madrid, Spain (T.P., L.B.).
  • Crespo J; Nutrition Department, Clínica las Condes, Santiago de Chile, Chile (R.A.).
  • Perez de Isla L; Fundación Hipercolesterolemia Familiar, Madrid, Spain (R.A., L.P.d.I., P.M.).
  • Mata P; From the Cardiovascular Science Institute - ICCC; IIB-Sant Pau, Hospital de Sant Pau, Barcelona, Spain (G.C.-B., T.P., J.C., L.B.).
  • Badimon L; Fundación Hipercolesterolemia Familiar, Madrid, Spain (R.A., L.P.d.I., P.M.).
Arterioscler Thromb Vasc Biol ; 39(5): 945-955, 2019 05.
Article en En | MEDLINE | ID: mdl-30866660
ABSTRACT
Objective- Heterozygous familial hypercholesterolemia (FH) is the most common genetic disorder associated with premature atherosclerotic cardiovascular disease. Circulating microvesicles (cMV) are released when cells are activated. We investigated whether cMV could provide information on coronary calcification and atherosclerosis in FH patients. Approach and Results- Eighty-two patients (mean of 44±9 years old) with molecular diagnosis of heterozygous FH and asymptomatic cardiovascular disease were investigated. Atherosclerotic plaque characterization was performed by computed tomography angiography, and Agatston coronary calcium score and plaque composition sum were calculated. cMV were quantified by flow cytometry using AV (annexin V) and cell surface-specific antibodies. Of the 82 FH patients, 48 presented atherosclerotic plaque. Patients with atherosclerosis were men and older in a higher percentage than patients without atherosclerotic plaque. FH patients with atherosclerotic plaque showed higher levels of total AV+ cMV, cMV AV+ from platelet origin, from granulocytes and neutrophils, and cMV AV+/- from endothelial cells than FH-patients without atherosclerotic plaque. Plaque composition sum correlated with platelet- and endothelial-derived cMV, and Agatston coronary calcium score correlated with granulocyte-, platelet-, and endothelial-derived cMV. Receiver operating characteristic curve analyses indicated that the cluster of platelet-, granulocyte-, neutrophil, and endothelial-derived cMV considered together, added significant predictive value to the specific SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) risk equation for plaque presence (area under the curve=0.866, 95% CI, 0.775-0.958; P<0.0001, P=0.030 for the increment of the area under the curve). Conclusions- Endothelial-, granulocyte-, neutrophil- and platelet-derived cMV discriminate and map coronary atherosclerotic plaque and calcification in asymptomatic patients with FH. Liquid biopsy of cMV may be a surrogate biomarker of coronary atherosclerotic plaque burden in FH patients.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de la Arteria Coronaria / Inhibidores de Hidroximetilglutaril-CoA Reductasas / Calcificación Vascular / Hiperlipoproteinemia Tipo II Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Arterioscler Thromb Vasc Biol Asunto de la revista: ANGIOLOGIA Año: 2019 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de la Arteria Coronaria / Inhibidores de Hidroximetilglutaril-CoA Reductasas / Calcificación Vascular / Hiperlipoproteinemia Tipo II Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Arterioscler Thromb Vasc Biol Asunto de la revista: ANGIOLOGIA Año: 2019 Tipo del documento: Article