Research progress of serum alkaline phosphatase in cardiovascular disease_West China Medical Journal

Authors：

XIONG Xing ¹ , WANG Zhimei ¹ , ZHANG Ning ¹ ,  WEN Xia ²

1. Inner Mongolia Clinical Medical College, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010020, P. R. China;
2. Department of Emergency, Inner Mongolia Autonomous Region People’s Hospital, Hohhot, Inner Mongolia 010020, P. R. China;

Corresponding author：

WEN Xia, Email: wenxia1982@126.com

Keywords：

Serum alkaline phosphatas; cardiovascular disease; dysfunction of endothelial cells in blood vessel; vascular calcification; cardiac fibrosis

DOI：

10.7507/1002-0179.202312064

Video：

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Abstract Full text Figures/Tables Video References Cited by

Serum alkaline phosphatase (ALP) has long been used as a biomarker for the liver, kidney, and bone. Currently, increasing evidence suggests a correlation between serum ALP and cardiovascular disease (CVD). Research has shown that serum ALP affects endothelial cell function and induces changes in pyrophosphate through various mechanisms to accelerate vascular calcification and promote cardiac fibrosis. Therefore, this article reviews the potential value of serum ALP in CVD through relevant research, revealing the specific relationship between serum ALP and CVD, in order to provide new ideas for the prevention and treatment of CVD.

Citation： XIONG Xing, WANG Zhimei, ZHANG Ning, WEN Xia. Research progress of serum alkaline phosphatase in cardiovascular disease. West China Medical Journal, 2024, 39(4): 645-648. doi: 10.7507/1002-0179.202312064 Copy

1.	Gan T, Hu J, Liu W, et al. Causal association between anemia and cardiovascular disease: a 2-sample bidirectional mendelian randomization study. J Am Heart Assoc, 2023, 12(12): e029689.
2.	Tsao CW, Aday AW, Almarzooq ZI, et al. Heart disease and stroke statistics-2022 update: a report from the American Heart Association. Circulation, 2022, 145(8): e153-e639.
3.	Paluch AE, Bajpai S, Ballin M, et al. Prospective association of daily steps with cardiovascular disease: a harmonized meta-analysis. Circulation, 2023, 147(2): 122-131.
4.	Guo W, Li X, Wu J, et al. Serum alkaline phosphatase is associated with arterial stiffness and 10-year cardiovascular disease risk in a Chinese population. Eur J Clin Invest, 2021, 51(8): e13560.
5.	Brichacek AL, Brown CM. Alkaline phosphatase: a potential biomarker for stroke and implications for treatment. Metab Brain Dis, 2019, 34(1): 3-19.
6.	Liu K, Yu Y, Yuan Y, et al. Elevated levels of serum alkaline phosphatase are associated with increased risk of cardiovascular disease: a prospective cohort study. J Atheroscler Thromb, 2023, 30(7): 795-819.
7.	Son DH, Ha HS, Lee YJ. Association of serum alkaline phosphatase with the TG/HDL ratio and TyG index in Korean adults. Biomolecules, 2021, 11(6): 882.
8.	Naito H, Nezu T, Hosomi N, et al. Increased serum alkaline phosphatase and functional outcome in patients with acute ischemic stroke presenting a low ankle-brachial index. J Atheroscler Thromb, 2022, 29(5): 719-730.
9.	Roszkowska M, Strzelecka-Kiliszek A, Bessueille L, et al. Collagen promotes matrix vesicle-mediated mineralization by vascular smooth muscle cells. J Inorg Biochem, 2018, 186: 1-9.
10.	Bottini M, Mebarek S, Anderson KL, Strzelecka-Kiliszek A, et al. Matrix vesicles from chondrocytes and osteoblasts: their biogenesis, properties, functions and biomimetic models. Biochim Biophys Acta Gen Subj, 2018, 1862(3): 532-546.
11.	Haarhaus M, Cianciolo G, Barbuto S, et al. Alkaline phosphatase: an old friend as treatment target for cardiovascular and mineral bone disorders in chronic kidney disease. Nutrients, 2022, 14(10): 2124.
12.	Ndrepepa G, Holdenrieder S, Cassese S, et al. A comparison of gamma-glutamyl transferase and alkaline phosphatase as prognostic markers in patients with coronary heart disease. Nutr Metab Cardiovasc Dis, 2018, 28(1): 64-70.
13.	Schoppet M, Shanahan CM. Role for alkaline phosphatase as an inducer of vascular calcification in renal failure?. Kidney Int, 2008, 73(9): 989-991.
14.	Dai XY, Zheng YY, Tang JN, et al. Alkaline phosphatase-to-albumin ratio as a novel predictor of long-term adverse outcomes in coronary artery disease patients who underwent PCI. Biosci Rep, 2021, 41(7): BSR20203904.
15.	Kim JH, Lee HS, Park HM, et al. Serum alkaline phosphatase level is positively associated with metabolic syndrome: a nationwide population-based study. Clin Chim Acta, 2020, 500: 189-194.
16.	Haarhaus M, Gilham D, Kulikowski E, et al. Pharmacologic epigenetic modulators of alkaline phosphatase in chronic kidney disease. Curr Opin Nephrol Hypertens, 2020, 29(1): 4-15.
17.	Seo MS, Shim JY, Lee YJ. Relationship between serum alkaline phosphatase level, C-reactive protein and leukocyte counts in adults aged 60 years or older. Scand J Clin Lab Invest, 2019, 79(4): 233-237.
18.	Lee JH, Lee JW, Lee YJ. The relationship between serum alkaline phosphatase and arterial stiffness in korean adults. J Atheroscler Thromb, 2019, 26(12): 1084-1091.
19.	Haarhaus M, Ray KK, Nicholls SJ, et al. Apabetalone lowers serum alkaline phosphatase and improves cardiovascular risk in patients with cardiovascular disease. Atherosclerosis, 2019, 290: 59-65.
20.	Haarhaus M, Brandenburg V, Kalantar-Zadeh K, et al. Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD. Nat Rev Nephrol, 2017, 13(7): 429-442.
21.	Qin Z, Li Y, Li J, et al. Exosomal STAT1 derived from high phosphorus-stimulated vascular endothelial cells induces vascular smooth muscle cell calcification via the Wnt/β-catenin signaling pathway. Int J Mol Med, 2022, 50(6): 139.
22.	Rodionov RN, Begmatov H, Jarzebska N, et al. Homoarginine supplementation prevents left ventricular dilatation and preserves systolic function in a model of coronary artery disease. J Am Heart Assoc, 2019, 8(14): e012486.
23.	Katzke V, Johnson T, Sookthai D, et al. Circulating liver enzymes and risks of chronic diseases and mortality in the prospective EPIC-heidelberg case-cohort study. BMJ Open, 2020, 10(3): e033532.
24.	Nelson AJ, Raggi P, Wolf M, et al. Targeting vascular calcification in chronic kidney disease. JACC Basic Transl Sci, 2020, 5(4): 398-412.
25.	Cheng X, Wang L, Wen X, et al. TNAP is a novel regulator of cardiac fibrosis after myocardial infarction by mediating TGF-β/Smads and ERK1/2 signaling pathways. EBioMedicine, 2021, 67: 103370.
26.	Ren Y, Li X, Wang S, et al. Serum alkaline phosphatase levels are associated with coronary artery calcification patterns and plaque vulnerability. Catheter Cardiovasc Interv, 2021, 97(Suppl 2): 1055-1062.
27.	Gao L, Wang LY, Liu ZQ, et al. TNAP inhibition attenuates cardiac fibrosis induced by myocardial infarction through deactivating TGF-β1/Smads and activating P53 signaling pathways. Cell Death Dis, 2020, 11(1): 44.
28.	Frangogiannis NG. Cardiac fibrosis: cell biological mechanisms, molecular pathways and therapeutic opportunities. Mol Aspects Med, 2019, 65: 70-99.
29.	Dixon IMC. Tissue non-specific alkaline phosphatase (TNAP): a player in post-MI cardiac fibrosis. EBioMedicine, 2021, 68: 103430.

1. Gan T, Hu J, Liu W, et al. Causal association between anemia and cardiovascular disease: a 2-sample bidirectional mendelian randomization study. J Am Heart Assoc, 2023, 12(12): e029689.
2. Tsao CW, Aday AW, Almarzooq ZI, et al. Heart disease and stroke statistics-2022 update: a report from the American Heart Association. Circulation, 2022, 145(8): e153-e639.
3. Paluch AE, Bajpai S, Ballin M, et al. Prospective association of daily steps with cardiovascular disease: a harmonized meta-analysis. Circulation, 2023, 147(2): 122-131.
4. Guo W, Li X, Wu J, et al. Serum alkaline phosphatase is associated with arterial stiffness and 10-year cardiovascular disease risk in a Chinese population. Eur J Clin Invest, 2021, 51(8): e13560.
5. Brichacek AL, Brown CM. Alkaline phosphatase: a potential biomarker for stroke and implications for treatment. Metab Brain Dis, 2019, 34(1): 3-19.
6. Liu K, Yu Y, Yuan Y, et al. Elevated levels of serum alkaline phosphatase are associated with increased risk of cardiovascular disease: a prospective cohort study. J Atheroscler Thromb, 2023, 30(7): 795-819.
7. Son DH, Ha HS, Lee YJ. Association of serum alkaline phosphatase with the TG/HDL ratio and TyG index in Korean adults. Biomolecules, 2021, 11(6): 882.
8. Naito H, Nezu T, Hosomi N, et al. Increased serum alkaline phosphatase and functional outcome in patients with acute ischemic stroke presenting a low ankle-brachial index. J Atheroscler Thromb, 2022, 29(5): 719-730.
9. Roszkowska M, Strzelecka-Kiliszek A, Bessueille L, et al. Collagen promotes matrix vesicle-mediated mineralization by vascular smooth muscle cells. J Inorg Biochem, 2018, 186: 1-9.
10. Bottini M, Mebarek S, Anderson KL, Strzelecka-Kiliszek A, et al. Matrix vesicles from chondrocytes and osteoblasts: their biogenesis, properties, functions and biomimetic models. Biochim Biophys Acta Gen Subj, 2018, 1862(3): 532-546.
11. Haarhaus M, Cianciolo G, Barbuto S, et al. Alkaline phosphatase: an old friend as treatment target for cardiovascular and mineral bone disorders in chronic kidney disease. Nutrients, 2022, 14(10): 2124.
12. Ndrepepa G, Holdenrieder S, Cassese S, et al. A comparison of gamma-glutamyl transferase and alkaline phosphatase as prognostic markers in patients with coronary heart disease. Nutr Metab Cardiovasc Dis, 2018, 28(1): 64-70.
13. Schoppet M, Shanahan CM. Role for alkaline phosphatase as an inducer of vascular calcification in renal failure?. Kidney Int, 2008, 73(9): 989-991.
14. Dai XY, Zheng YY, Tang JN, et al. Alkaline phosphatase-to-albumin ratio as a novel predictor of long-term adverse outcomes in coronary artery disease patients who underwent PCI. Biosci Rep, 2021, 41(7): BSR20203904.
15. Kim JH, Lee HS, Park HM, et al. Serum alkaline phosphatase level is positively associated with metabolic syndrome: a nationwide population-based study. Clin Chim Acta, 2020, 500: 189-194.
16. Haarhaus M, Gilham D, Kulikowski E, et al. Pharmacologic epigenetic modulators of alkaline phosphatase in chronic kidney disease. Curr Opin Nephrol Hypertens, 2020, 29(1): 4-15.
17. Seo MS, Shim JY, Lee YJ. Relationship between serum alkaline phosphatase level, C-reactive protein and leukocyte counts in adults aged 60 years or older. Scand J Clin Lab Invest, 2019, 79(4): 233-237.
18. Lee JH, Lee JW, Lee YJ. The relationship between serum alkaline phosphatase and arterial stiffness in korean adults. J Atheroscler Thromb, 2019, 26(12): 1084-1091.
19. Haarhaus M, Ray KK, Nicholls SJ, et al. Apabetalone lowers serum alkaline phosphatase and improves cardiovascular risk in patients with cardiovascular disease. Atherosclerosis, 2019, 290: 59-65.
20. Haarhaus M, Brandenburg V, Kalantar-Zadeh K, et al. Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD. Nat Rev Nephrol, 2017, 13(7): 429-442.
21. Qin Z, Li Y, Li J, et al. Exosomal STAT1 derived from high phosphorus-stimulated vascular endothelial cells induces vascular smooth muscle cell calcification via the Wnt/β-catenin signaling pathway. Int J Mol Med, 2022, 50(6): 139.
22. Rodionov RN, Begmatov H, Jarzebska N, et al. Homoarginine supplementation prevents left ventricular dilatation and preserves systolic function in a model of coronary artery disease. J Am Heart Assoc, 2019, 8(14): e012486.
23. Katzke V, Johnson T, Sookthai D, et al. Circulating liver enzymes and risks of chronic diseases and mortality in the prospective EPIC-heidelberg case-cohort study. BMJ Open, 2020, 10(3): e033532.
24. Nelson AJ, Raggi P, Wolf M, et al. Targeting vascular calcification in chronic kidney disease. JACC Basic Transl Sci, 2020, 5(4): 398-412.
25. Cheng X, Wang L, Wen X, et al. TNAP is a novel regulator of cardiac fibrosis after myocardial infarction by mediating TGF-β/Smads and ERK1/2 signaling pathways. EBioMedicine, 2021, 67: 103370.
26. Ren Y, Li X, Wang S, et al. Serum alkaline phosphatase levels are associated with coronary artery calcification patterns and plaque vulnerability. Catheter Cardiovasc Interv, 2021, 97(Suppl 2): 1055-1062.
27. Gao L, Wang LY, Liu ZQ, et al. TNAP inhibition attenuates cardiac fibrosis induced by myocardial infarction through deactivating TGF-β1/Smads and activating P53 signaling pathways. Cell Death Dis, 2020, 11(1): 44.
28. Frangogiannis NG. Cardiac fibrosis: cell biological mechanisms, molecular pathways and therapeutic opportunities. Mol Aspects Med, 2019, 65: 70-99.
29. Dixon IMC. Tissue non-specific alkaline phosphatase (TNAP): a player in post-MI cardiac fibrosis. EBioMedicine, 2021, 68: 103430.

West China Medical Journal

Research progress of serum alkaline phosphatase in cardiovascular disease

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