Altered Functionality of Lipoprotein(a) Impacts on Angiogenesis in Diabetic Retinopathy.

Autor:	Shariatzadeh M; Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands., Nagtzaam NMA; Laboratory Medical Immunology, Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands., van Vark-van der Zee L; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands., van Holten-Neelen C; Laboratory Medical Immunology, Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands., Verhoeven AJM; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands., Dehairs J; Department of Oncology, Laboratory of Lipid Metabolism and Cancer, KU Leuven - University of Leuven, Leuven, Belgium., Swinnen JV; Department of Oncology, Laboratory of Lipid Metabolism and Cancer, KU Leuven - University of Leuven, Leuven, Belgium., Leijten F; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands., Ten Berge JC; Department of Ophthalmology, Erasmus University Medical Center, Rotterdam, The Netherlands., Ciriano JPM; Rotterdam Eye Hospital, Rotterdam, The Netherlands., Wong KT; Rotterdam Eye Hospital, Rotterdam, The Netherlands., Mulder M; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands., Leenen PJM; Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands., Dik WA; Laboratory Medical Immunology, Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2023 May 01; Vol. 64 (5), pp. 8.
DOI:	10.1167/iovs.64.5.8
Abstrakt:	Purpose: Diabetic retinopathy (DR) is a complication of type 2 diabetes mellitus (T2DM). Lipoprotein(a) (Lp(a)) contributes to the progression of DR, but how is unclear. In homeostasis of the retinal microvasculature, myeloid-derived pro-angiogenic cells (PACs) also play a pivotal role, and fail to function properly in diabetic conditions. Here, we explored the putative contribution of Lp(a) from patients with T2DM with/without DR and healthy controls on inflammation and angiogenesis of retinal endothelial cells (RECs), and on PAC differentiation. Subsequently, we compared the lipid composition of Lp(a) from patients to that from healthy controls. Methods: Lp(a)/LDL obtained from patients and healthy controls were added to TNF-alpha-activated RECs. Expression of VCAM-1/ICAM-1 was measured using flowcytometry. Angiogenesis was determined in REC-pericyte co-cultures stimulated by pro-angiogenic growth factors. PAC differentiation from peripheral blood mononuclear cells was determined by measuring expression of PAC markers. The lipoprotein lipid composition was quantified using detailed lipidomics analysis. Results: Lp(a) from patients with DR (DR-Lp(a)) failed to block TNF-alpha-induced expression of VCAM-1/ICAM-1 in REC whereas Lp(a) from healthy controls (healthy control [HC]-Lp(a)) did. DR-Lp(a) increased REC angiogenesis more than HC-Lp(a) did. Lp(a) from patients without DR showed intermediate profiles. HC-Lp(a) reduced the expression of CD16 and CD105 in PAC, but T2DM-Lp(a) did not. Phosphatidylethanolamine content was lower in T2DM-Lp(a) than in HC-Lp(a). Conclusions: DR-Lp(a) does not show the anti-inflammatory capacity seen with HC-Lp(a), but increases REC angiogenesis, and affects PAC differentiation less than HC-Lp(a). These functional differences in Lp(a) in T2DM-related retinopathy are associated with alterations in the lipid composition as compared to healthy conditions.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu