Vascular Collagen Type-IV in Hypertension and Cerebral Small Vessel Disease.

Autor:	Kumar AA; Molecular and Clinical Sciences Research Institute, St George's University of London, United Kingdom (A.A.K., N.Y., M.W., P.A., T.R.B., L.R.B., D.N.M., A.C.P., G.P., A.B.S., A.H.H.).; Neurology (A.A.K., A.C.P., A.H.H.), St George's University Hospitals NHS Foundation Trust, London, United Kingdom., Yeo N; Molecular and Clinical Sciences Research Institute, St George's University of London, United Kingdom (A.A.K., N.Y., M.W., P.A., T.R.B., L.R.B., D.N.M., A.C.P., G.P., A.B.S., A.H.H.)., Whittaker M; Molecular and Clinical Sciences Research Institute, St George's University of London, United Kingdom (A.A.K., N.Y., M.W., P.A., T.R.B., L.R.B., D.N.M., A.C.P., G.P., A.B.S., A.H.H.)., Attra P; Molecular and Clinical Sciences Research Institute, St George's University of London, United Kingdom (A.A.K., N.Y., M.W., P.A., T.R.B., L.R.B., D.N.M., A.C.P., G.P., A.B.S., A.H.H.)., Barrick TR; Molecular and Clinical Sciences Research Institute, St George's University of London, United Kingdom (A.A.K., N.Y., M.W., P.A., T.R.B., L.R.B., D.N.M., A.C.P., G.P., A.B.S., A.H.H.)., Bridges LR; Molecular and Clinical Sciences Research Institute, St George's University of London, United Kingdom (A.A.K., N.Y., M.W., P.A., T.R.B., L.R.B., D.N.M., A.C.P., G.P., A.B.S., A.H.H.).; Cellular Pathology (L.R.B.), St George's University Hospitals NHS Foundation Trust, London, United Kingdom., Dickson DW; Department of Neuroscience, Mayo Clinic, Jacksonville, FL (D.W.D., W.L.L.)., Esiri MM; Nuffield Department of Clinical Neurosciences, Oxford University, United Kingdom (M.M.E., G.Z.)., Farris CW; Department of Anatomy and Neurobiology, Boston University School of Medicine, MA (C.W.F., D.L.R.)., Graham D; Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (D.G., T.V.A.)., Lin WL; Department of Neuroscience, Mayo Clinic, Jacksonville, FL (D.W.D., W.L.L.)., Meijles DN; Molecular and Clinical Sciences Research Institute, St George's University of London, United Kingdom (A.A.K., N.Y., M.W., P.A., T.R.B., L.R.B., D.N.M., A.C.P., G.P., A.B.S., A.H.H.)., Pereira AC; Molecular and Clinical Sciences Research Institute, St George's University of London, United Kingdom (A.A.K., N.Y., M.W., P.A., T.R.B., L.R.B., D.N.M., A.C.P., G.P., A.B.S., A.H.H.).; Neurology (A.A.K., A.C.P., A.H.H.), St George's University Hospitals NHS Foundation Trust, London, United Kingdom., Perry G; Molecular and Clinical Sciences Research Institute, St George's University of London, United Kingdom (A.A.K., N.Y., M.W., P.A., T.R.B., L.R.B., D.N.M., A.C.P., G.P., A.B.S., A.H.H.)., Rosene DL; Department of Anatomy and Neurobiology, Boston University School of Medicine, MA (C.W.F., D.L.R.)., Shtaya AB; Molecular and Clinical Sciences Research Institute, St George's University of London, United Kingdom (A.A.K., N.Y., M.W., P.A., T.R.B., L.R.B., D.N.M., A.C.P., G.P., A.B.S., A.H.H.)., Van Agtmael T; Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (D.G., T.V.A.)., Zamboni G; Nuffield Department of Clinical Neurosciences, Oxford University, United Kingdom (M.M.E., G.Z.).; Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Università di Modena e Reggio Emilia, Italy (G.Z.)., Hainsworth AH; Molecular and Clinical Sciences Research Institute, St George's University of London, United Kingdom (A.A.K., N.Y., M.W., P.A., T.R.B., L.R.B., D.N.M., A.C.P., G.P., A.B.S., A.H.H.).; Neurology (A.A.K., A.C.P., A.H.H.), St George's University Hospitals NHS Foundation Trust, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Stroke [Stroke] 2022 Dec; Vol. 53 (12), pp. 3696-3705. Date of Electronic Publication: 2022 Oct 07.
DOI:	10.1161/STROKEAHA.122.037761
Abstrakt:	Background: Cerebral small vessel disease (SVD) is common in older people and causes lacunar stroke and vascular cognitive impairment. Risk factors include old age, hypertension and variants in the genes COL4A1/COL4A2 encoding collagen alpha-1(IV) and alpha-2(IV), here termed collagen-IV, which are core components of the basement membrane. We tested the hypothesis that increased vascular collagen-IV associates with clinical hypertension and with SVD in older persons and with chronic hypertension in young and aged primates and genetically hypertensive rats. Methods: We quantified vascular collagen-IV immunolabeling in small arteries in a cohort of older persons with minimal Alzheimer pathology (N=52; 21F/31M, age 82.8±6.95 years). We also studied archive tissue from young (age range 6.2-8.3 years) and older (17.0-22.7 years) primates ( M mulatta ) and compared chronically hypertensive animals (18 months aortic stenosis) with normotensives. We also compared genetically hypertensive and normotensive rats (aged 10-12 months). Results: Collagen-IV immunolabeling in cerebral small arteries of older persons was negatively associated with radiological SVD severity (ρ: -0.427, P =0.005) but was not related to history of hypertension. General linear models confirmed the negative association of lower collagen-IV with radiological SVD ( P <0.017), including age as a covariate and either clinical hypertension ( P <0.030) or neuropathological SVD diagnosis ( P <0.022) as fixed factors. Reduced vascular collagen-IV was accompanied by accumulation of fibrillar collagens (types I and III) as indicated by immunogold electron microscopy. In young and aged primates, brain collagen-IV was elevated in older normotensive relative to young normotensive animals ( P =0.029) but was not associated with hypertension. Genetically hypertensive rats did not differ from normotensive rats in terms of arterial collagen-IV. Conclusions: Our cross-species data provide novel insight into sporadic SVD pathogenesis, supporting insufficient (rather than excessive) arterial collagen-IV in SVD, accompanied by matrix remodeling with elevated fibrillar collagen deposition. They also indicate that hypertension, a major risk factor for SVD, does not act by causing accumulation of brain vascular collagen-IV.
Databáze:	MEDLINE
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