Is Lysosomal Acid Lipase Activity Associated with the Presence and Severity of Coronary Artery Disease?

Overview

Journal Herz

Specialty Cardiology & Vascular Diseases

Date 2023 Aug 1

PMID 37528297

Authors

Emrullah Kiziltunc

Sabire Gokalp

Gursel Biberoglu

Yakup Yalcin

Burcu Cihan

Ridvan M Oktem

Asli Inci

Leyla Tumer

Mehmet R Yalcin

Adnan Abaci

Affiliations

Soon will be listed here.

Abstract

Background: Lipid metabolism is considerably complex and there can be many critical steps in atherogenesis. The association between lysosomal acid lipase (LAL) activity and coronary artery disease (CAD) has not been elucidated in detail. We aimed to evaluate the association between LAL activity with the presence and severity of CAD in patients who are seen in daily clinical practice.

Methods: Patients who underwent coronary angiography were divided into groups according to the angiography results. Syntax scores and Gensini scores were calculated. The LAL activity was measured from dried blood spots.

Results: Median LAL activity values were similar in all study groups (normal coronary arteries: 0.40 nmol/punch/h; non-obstructive CAD: 0.44 nmol/punch/h; obstructive chronic CAD: 0.40 nmol/punch/h; obstructive acute coronary syndrome: 0.48 nmol/punch/h) and there was no correlation between coronary atherosclerotic burden and LAL activity (correlation coefficients Syntax score and LAL: -0.032; Gensini score and LAL: -0.030). In addition, no relationship between serum lipid levels and LAL activity was detected.

Conclusion: The presence of CAD and its severity is not associated with the LAL activity in patients encountered in daily clinical practice.

References

Crisby M, Shah P, Yano J, Zhu J, Nilsson J . Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation. 2001; 103(7):926-33. DOI: 10.1161/01.cir.103.7.926. View

Gao F, Wang Z, Ma X, Shen H, Yang L, Zhou Y . Effect of alirocumab on coronary plaque in patients with coronary artery disease assessed by optical coherence tomography. Lipids Health Dis. 2021; 20(1):106. PMC: 8436513. DOI: 10.1186/s12944-021-01528-3. View

Visseren F, Mach F, Smulders Y, Carballo D, Koskinas K, Back M . 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021; 42(34):3227-3337. DOI: 10.1093/eurheartj/ehab484. View

Pericleous M, Kelly C, Wang T, Livingstone C, Ala A . Wolman's disease and cholesteryl ester storage disorder: the phenotypic spectrum of lysosomal acid lipase deficiency. Lancet Gastroenterol Hepatol. 2017; 2(9):670-679. DOI: 10.1016/S2468-1253(17)30052-3. View

Bernstein D, Hulkova H, Bialer M, Desnick R . Cholesteryl ester storage disease: review of the findings in 135 reported patients with an underdiagnosed disease. J Hepatol. 2013; 58(6):1230-43. DOI: 10.1016/j.jhep.2013.02.014. View

Du H, Schiavi S, Wan N, Levine M, Witte D, Grabowski G . Reduction of atherosclerotic plaques by lysosomal acid lipase supplementation. Arterioscler Thromb Vasc Biol. 2003; 24(1):147-54. DOI: 10.1161/01.ATV.0000107030.22053.1e. View

Sun Y, Xu Y, Du H, Quinn B, Liou B, Stanton L . Reversal of advanced disease in lysosomal acid lipase deficient mice: a model for lysosomal acid lipase deficiency disease. Mol Genet Metab. 2014; 112(3):229-41. DOI: 10.1016/j.ymgme.2014.04.006. View

Hamilton J, Jones I, Srivastava R, Galloway P . A new method for the measurement of lysosomal acid lipase in dried blood spots using the inhibitor Lalistat 2. Clin Chim Acta. 2012; 413(15-16):1207-10. DOI: 10.1016/j.cca.2012.03.019. View

Neeland I, Patel R, Eshtehardi P, Dhawan S, McDaniel M, Rab S . Coronary angiographic scoring systems: an evaluation of their equivalence and validity. Am Heart J. 2012; 164(4):547-552.e1. PMC: 3913177. DOI: 10.1016/j.ahj.2012.07.007. View

10.

Zhang H . Lysosomal acid lipase and lipid metabolism: new mechanisms, new questions, and new therapies. Curr Opin Lipidol. 2018; 29(3):218-223. PMC: 6215475. DOI: 10.1097/MOL.0000000000000507. View

11.

Dubland J, Francis G . Lysosomal acid lipase: at the crossroads of normal and atherogenic cholesterol metabolism. Front Cell Dev Biol. 2015; 3:3. PMC: 4313778. DOI: 10.3389/fcell.2015.00003. View

12.

Zhang H, Reilly M . Variants in Genome-Wide Association Studies of Coronary Artery Diseases: Loss-of-Function or Gain-of-Function?. Arterioscler Thromb Vasc Biol. 2017; 37(6):1015-1017. PMC: 5526101. DOI: 10.1161/ATVBAHA.117.309344. View

13.

Du H, Schiavi S, Levine M, Mishra J, Heur M, Grabowski G . Enzyme therapy for lysosomal acid lipase deficiency in the mouse. Hum Mol Genet. 2001; 10(16):1639-48. DOI: 10.1093/hmg/10.16.1639. View

14.

Haley N, Fowler S, DE DUVE C . Lysosomal acid cholesteryl esterase activity in normal and lipid-laden aortic cells. J Lipid Res. 1980; 21(8):961-9. View

15.

Ries S, Buchler C, Langmann T, Fehringer P, Aslanidis C, Schmitz G . Transcriptional regulation of lysosomal acid lipase in differentiating monocytes is mediated by transcription factors Sp1 and AP-2. J Lipid Res. 1998; 39(11):2125-34. View

16.

Davis H, Glagov S, Zarins C . Role of acid lipase in cholesteryl ester accumulation during atherogenesis. Correlation of enzyme activity with acid lipase-containing macrophages in rabbit and human lesions. Atherosclerosis. 1985; 55(2):205-15. DOI: 10.1016/0021-9150(85)90099-1. View

17.

Wild P, Zeller T, Schillert A, Szymczak S, Sinning C, Deiseroth A . A genome-wide association study identifies LIPA as a susceptibility gene for coronary artery disease. Circ Cardiovasc Genet. 2011; 4(4):403-12. PMC: 3157552. DOI: 10.1161/CIRCGENETICS.110.958728. View

18.

Coates P, Langer T, CORTNER J . Genetic variation of human mononuclear leukocyte lysosomal acid lipase activity. Relationship to atherosclerosis. Atherosclerosis. 1986; 62(1):11-20. DOI: 10.1016/0021-9150(86)90014-6. View

19.

Lukacs Z, Barr M, Hamilton J . Best practice in the measurement and interpretation of lysosomal acid lipase in dried blood spots using the inhibitor Lalistat 2. Clin Chim Acta. 2017; 471:201-205. DOI: 10.1016/j.cca.2017.05.027. View

20.

Hong X, Chen Y, Barr M, Gelb M . Stratification of patients with lysosomal acid lipase deficiency by enzyme activity in dried blood spots. Mol Genet Metab Rep. 2022; 33:100935. PMC: 9664517. DOI: 10.1016/j.ymgmr.2022.100935. View