Increased high‑density lipoprotein‑oxidant index in ischemic stroke patients

Damayanthi,Deepa; Krishnamoorthy,Soumya; Sylaja,P.Ν.; Gopala,Srinivas

doi:10.3892/br.2022.1570

Increased high‑density lipoprotein‑oxidant index in ischemic stroke patients

Authors:
- Deepa Damayanthi
- Soumya Krishnamoorthy
- P.Ν. Sylaja
- Srinivas Gopala
View Affiliations

Affiliations: Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala 695011, India, Comprehensive Stroke Program, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala 695011, India
Published online on: September 14, 2022 https://doi.org/10.3892/br.2022.1570
Article Number: 87

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

High‑density lipoprotein (HDL) is known to have atheroprotective properties which could become dysfunctional under certain disease conditions, particularly during the atherosclerotic progression. The present study sought to assess HDL functionality in acute ischemic stroke (AIS) patients in comparison with controls and the functional alteration among the ischemic stroke subtypes. The HDL functionality was evaluated in 71 statin‑naïve, adult patients of South Indian descent, admitted with AIS and were compared with that of 25 age‑ and sex‑matched healthy volunteers. Functional assay of HDL was based on its antioxidant ability to inhibit low‑density lipoproteins (LDL) oxidation by air using a dichlorodihydrofluorescein‑based fluorescent assay and expressed as HDL oxidant index (HOI). The HOI was higher in ischemic stroke patients as compared with controls (1.07±0.32 vs. 0.51±0.12; P<0.001) indicating high oxidative stress and dysfunctionality in HDL. Regarding the stroke subtypes, HOI was >1 in all stroke subtypes: 1.05±0.301 for Cardioembolic subtype, 1.15±0.41 for large vessel disease, and 1.01±0.25 for small vessel disease when compared with controls. However, no significant difference was noted in HOI values among the three stroke subtypes in the post hoc analysis. It was found that HDL in all ischemic stroke subtypes had less antioxidant capacity, indicating dysfunctional HDL. Functional alteration occurred in HDL of patients even in the presence of normal HDL‑cholesterol levels suggesting that dysfunctionality in HDL is unrelated to cholesterol content.

View Figures

View References

1	Jovin TG, Demchuk AM and Gupta R: Pathophysiology of Acute Ischemic Stroke. Continuum (Minneap Minn). 14:28–45. 2008.
2	Eren E, Yilmaz N and Aydin O: High density lipoprotein and it's dysfunction. Open Biochem J. 6:78–93. 2012.PubMed/NCBI View Article : Google Scholar
3	Shao B and Heinecke JW: HDL, lipid peroxidation, and atherosclerosis. J Lipid Res. 50:599–601. 2009.PubMed/NCBI View Article : Google Scholar
4	Lee SH, Kim HS, Park YM, Kwon HS, Yoon KH, Han K and Kim MK: HDL-cholesterol, its variability, and the risk of diabetes: A nationwide population-based study. J Clin Endocrinol Metab. 104:5633–5641. 2019.PubMed/NCBI View Article : Google Scholar
5	Kosmas CE, Martinez I, Sourlas A, Bouza KV, Campos FN, Torres V, Montan PD and Guzman E: High-density lipoprotein (HDL) functionality and its relevance to atherosclerotic cardiovascular disease. Drugs Context. 7(212525)2018.PubMed/NCBI View Article : Google Scholar
6	Sini S, Deepa D, Harikrishnan S and Jayakumari N: Evidence for an exclusive association of matrix metalloproteinase-9 with dysfunctional high-density lipoprotein: A novel finding. Atherosclerosis. 236:162–168. 2014.PubMed/NCBI View Article : Google Scholar
7	Sanossian N, Saver JL, Navab M and Ovbiagele B: High-density lipoprotein cholesterol: An emerging target for stroke treatment. Stroke. 38:1104–1109. 2007.PubMed/NCBI View Article : Google Scholar
8	Ansell BJ, Navab M, Hama S, Kamranpour N, Fonarow G, Hough G, Rahmani S, Mottahedeh R, Dave R, Reddy ST and Fogelman AM: Inflammatory/antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment. Circulation. 108:2751–2756. 2003.PubMed/NCBI View Article : Google Scholar
9	Kalani R, Krishnamoorthy S, Deepa D, Gopala S, Prabhakaran D, Tirschwell D and Sylaja PN: Apolipoproteins B and A1 in Ischemic Stroke Subtypes. J Stroke Cerebrovasc Dis. 29(104670)2020.PubMed/NCBI View Article : Google Scholar
10	Krishnamoorthy S, Damayanthi D, Gopala S, Paul R and Sylaja PN: High-sensitivity C-reactive protein and lipoprotein-associated phospholipase A2 in predicting recurrence and severity of stenosis in symptomatic intracranial atherosclerotic disease. Curr Proteomics. 18:231–236. 2021.
11	Tang X, Mao L, Chen J, Zhang T, Weng S, Guo X, Kuang J, Yu B and Peng D: High-sensitivity CRP may be a marker of HDL dysfunction and remodeling in patients with acute coronary syndrome. Sci Rep. 11(11444)2021.PubMed/NCBI View Article : Google Scholar
12	Shahar E, Chambless LE, Rosamond WD, Boland LL, Ballantyne CM, McGovern PG and Sharrett AR: Atherosclerosis Risk in Communities Study. Plasma lipid profile and incident ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study. Stroke. 34:623–631. 2003.PubMed/NCBI View Article : Google Scholar
13	Zhang Y, Tuomilehto J, Jousilahti P, Wang Y, Antikainen R and Hu G: Total and high-density lipoprotein cholesterol and stroke risk. Stroke. 43:1768–1774. 2012.PubMed/NCBI View Article : Google Scholar
14	Woodward M, Barzi F, Feigin V, Gu D, Huxley R, Nakamura K, Patel A, Ho S and Jamrozik K: Asia Pacific Cohort Studies Collaboration. Associations between high-density lipoprotein cholesterol and both stroke and coronary heart disease in the Asia Pacific region. Eur Heart J. 28:2653–2660. 2007.PubMed/NCBI View Article : Google Scholar
15	Amarenco P, Labreuche J and Touboul PJ: High-density lipoprotein-cholesterol and risk of stroke and carotid atherosclerosis: A systematic review. Atherosclerosis. 196:489–496. 2008.PubMed/NCBI View Article : Google Scholar
16	Sacco RL, Benson RT, Kargman DE, Boden-Albala B, Tuck C, Lin IF, Cheng JF, Paik MC, Shea S and Berglund L: High-density lipoprotein cholesterol and ischemic stroke in the elderly: The northern Manhattan stroke study. JAMA. 285:2729–2735. 2001.PubMed/NCBI View Article : Google Scholar
17	Ortiz-Munoz G, Couret D, Lapergue B, Bruckert E, Meseguer E, Amarenco P and Meilhac O: Dysfunctional HDL in acute stroke. Atherosclerosis. 253:75–80. 2016.PubMed/NCBI View Article : Google Scholar
18	Varela LM, Meseguer E, Lapergue B, Couret D, Amarenco P and Meilhac O: Changes in high-density lipoproteins related to outcomes in patients with acute stroke. J Clin Med. 9(2269)2020.PubMed/NCBI View Article : Google Scholar
19	Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL and Marsh EE III: Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in acute stroke treatment. Stroke. 24:35–41. 1993.PubMed/NCBI View Article : Google Scholar
20	Rankin J: Cerebral vascular accidents in patients over the age of 60: II. Prognosis. Scott Med J. 2:200–215. 1957.PubMed/NCBI View Article : Google Scholar
21	Femlak M, Gluba-Brzózka A, Ciałkowska-Rysz A and Rysz J: The role and function of HDL in patients with diabetes mellitus and the related cardiovascular risk. Lipids Health Dis. 16(207)2017.PubMed/NCBI View Article : Google Scholar
22	Izzo C, Grillo F and Murador E: Improved method for determination of high-density-lipoprotein cholesterol I. Isolation of high-density lipoproteins by use of polyethylene glycol 6000. Clin Chem. 27:371–374. 1981.PubMed/NCBI
23	Chapman MJ, Goldstein S, Lagrange D and Laplaud PM: A density gradient ultracentrifugal procedure for the isolation of the major lipoprotein classes from human serum. J Lipid Res. 22:339–358. 1981.PubMed/NCBI
24	Navab M, Yu R, Gharavi N, Huang W, Ezra N, Lotfizadeh A, Anantharamaiah GM, Alipour N, Van Lenten BJ, Reddy ST and Marelli D: High-density lipoprotein: Antioxidant and anti-inflammatory properties. Curr Atheroscler Rep. 9:244–248. 2007.PubMed/NCBI View Article : Google Scholar
25	Yin F, Ramanathan G, Zhang M and Araujo JA: Prooxidative effects of ambient pollutant chemicals are inhibited by HDL. J Biochem Mol Toxicol. 27:172–183. 2013.PubMed/NCBI View Article : Google Scholar
26	Breton CV, Yin F, Wang X, Avol E, Gilliland FD and Araujo JA: HDL anti-oxidant function associates with LDL level in young adults. Atherosclerosis. 232:165–170. 2014.PubMed/NCBI View Article : Google Scholar
27	Singh K, Chandra A, Sperry T, Joshi PH, Khera A, Virani SS, Ballantyne CM, Otvos JD, Dullaart RPF, Gruppen EG, et al: Associations between high-density lipoprotein particles and Ischemic events by vascular domain, sex, and ethnicity: A pooled cohort analysis. Circulation. 142:657–669. 2020.PubMed/NCBI View Article : Google Scholar
28	Ross R: Atherosclerosis-an inflammatory disease. N Engl J Med. 340:115–126. 1999.PubMed/NCBI View Article : Google Scholar
29	Duparc T, Ruidavets JB, Genoux A, Ingueneau C, Najib S, Ferrières J, Perret B and Martinez LO: Serum level of HDL particles are independently associated with long-term prognosis in patients with coronary artery disease: The GENES study. Sci Rep. 10(8138)2020.PubMed/NCBI View Article : Google Scholar
30	Sini S and Jayakumari N: Functionally defective high density lipoprotein is pro-oxidant: A deviation from normal atheroprotective character. Int J Nutr Food Sci. 2:92–101. 2013.
31	Feingold KR and Grunfeld C: Effect of inflammation on HDL structure and function. Curr Opin Lipidol. 27:521–530. 2016.PubMed/NCBI View Article : Google Scholar
32	Lapergue B, Moreno JA, Dang BQ, Coutard M, Delbosc S, Raphaeli G, Auge N, Klein I, Mazighi M, Michel JB, et al: Protective effect of high-density lipoprotein-based therapy in a model of embolic stroke. Stroke. 41:1536–1542. 2010.PubMed/NCBI View Article : Google Scholar
33	Kaul S, Alladi S, Jabeen SA, Bandaru VCSSR, Ankem U, Mekala S and Naik GS: Intracranial atherosclerosis is the most common stroke subtype: Ten-year data from Hyderabad stroke registry (India). Ann Indian Acad Neurol. 21:209–213. 2018.PubMed/NCBI View Article : Google Scholar