BACKGROUND: Ultrastructural findings of idiopathic dilated cardiomyopathy (IDCM) include myocyte atrophy and myofilament loss, yet little is known about the vascular abnormalities present in IDCM. METHODS AND RESULTS: Patients with IDCM and controls underwent multi-slice CT to examine length and diameter of epicardial vasculature. The levels of mobilizing cytokines and circulating EPCs were assessed by endothelial colony formation assay and flow cytometry. Immunohistochemistry and Western blot were used to examine microvessel density and expression of HIF-1alpha and beta-catenin. Main epicardial coronary arteries were shorter and smaller, and microvascular density was reduced in the epicardium in IDCM. Epicardial vessel paucity was associated with increased numbers of HIF-1alpha(+) cells (46.8+/-13.1% vs. 19.4+/-9.4%, p=0.006) indicating local epicardial hypoxia and elevation of circulating VEGF-A (394 pg/mL vs. 22 pg/mL, p=0.001). The number of mobilized progenitors CD133(+)/VEGF-R2(+) was 21-fold higher in IDCM compared with controls (6.5+/-3.3% vs. 0.3+/-0.2%; p<0.001). Moreover, this defective vascularization was associated with reduced myocardial expression of vascular beta-catenin, an important angiogenic regulator. CONCLUSIONS: This study shows defective vascularization and impaired vasculogenesis (the de novo vascular organization of mobilized endothelial progenitors) and angiogenesis (by which new blood vessels are formed from pre-existing mature endothelial cells) in human IDCM.
BACKGROUND: Ultrastructural findings of idiopathic dilated cardiomyopathy (IDCM) include myocyte atrophy and myofilament loss, yet little is known about the vascular abnormalities present in IDCM. METHODS AND RESULTS:Patients with IDCM and controls underwent multi-slice CT to examine length and diameter of epicardial vasculature. The levels of mobilizing cytokines and circulating EPCs were assessed by endothelial colony formation assay and flow cytometry. Immunohistochemistry and Western blot were used to examine microvessel density and expression of HIF-1alpha and beta-catenin. Main epicardial coronary arteries were shorter and smaller, and microvascular density was reduced in the epicardium in IDCM. Epicardial vessel paucity was associated with increased numbers of HIF-1alpha(+) cells (46.8+/-13.1% vs. 19.4+/-9.4%, p=0.006) indicating local epicardial hypoxia and elevation of circulating VEGF-A (394 pg/mL vs. 22 pg/mL, p=0.001). The number of mobilized progenitors CD133(+)/VEGF-R2(+) was 21-fold higher in IDCM compared with controls (6.5+/-3.3% vs. 0.3+/-0.2%; p<0.001). Moreover, this defective vascularization was associated with reduced myocardial expression of vascular beta-catenin, an important angiogenic regulator. CONCLUSIONS: This study shows defective vascularization and impaired vasculogenesis (the de novo vascular organization of mobilized endothelial progenitors) and angiogenesis (by which new blood vessels are formed from pre-existing mature endothelial cells) in human IDCM.
Authors: Piotr Sklepkiewicz; Takayuki Shiomi; Rajbir Kaur; Jie Sun; Susan Kwon; Becky Mercer; Peter Bodine; Ralph Theo Schermuly; Isaac George; P Christian Schulze; Jeanine M D'Armiento Journal: Circ Heart Fail Date: 2015-02-10 Impact factor: 8.790
Authors: Hilde M Norum; Kaspar Broch; Annika E Michelsen; Ida G Lunde; Tove Lekva; Aurelija Abraityte; Christen P Dahl; Arnt E Fiane; Arne K Andreassen; Geir Christensen; Svend Aakhus; Pål Aukrust; Lars Gullestad; Thor Ueland Journal: J Cardiovasc Transl Res Date: 2017-05-04 Impact factor: 4.132
Authors: Ayman Samman Tahhan; Muhammad Hammadah; Pratik B Sandesara; Salim S Hayek; Andreas P Kalogeropoulos; Ayman Alkhoder; Heval Mohamed Kelli; Matthew Topel; Nima Ghasemzadeh; Kaavya Chivukula; Yi-An Ko; Hiroshi Aida; Iraj Hesaroieh; Ernestine Mahar; Jonathan H Kim; Peter Wilson; Leslee Shaw; Viola Vaccarino; Edmund K Waller; Arshed A Quyyumi Journal: Circ Heart Fail Date: 2017-08-08 Impact factor: 8.790
Authors: Santiago Roura; Carolina Gálvez-Montón; Marco A Fernández; Josep Lupón; Antoni Bayes-Genis Journal: J Cardiovasc Transl Res Date: 2016-01-06 Impact factor: 4.132
Authors: Santiago Roura; Juli R Bagó; Carolina Soler-Botija; Josep M Pujal; Carolina Gálvez-Montón; Cristina Prat-Vidal; Aida Llucià-Valldeperas; Jerónimo Blanco; Antoni Bayes-Genis Journal: PLoS One Date: 2012-11-16 Impact factor: 3.240