Implications of the Serum Concentrations of Neuregulin-4 (Nrg4) in Patients with Coronary Artery Disease: A Case-Control Study
-
Fatemeh Taheri
,
Mohammad Javad Hosseinzadeh-Attar
,
Elham Alipoor
,
Elaheh Honarkar-Shafie
,
Mehdi Yaseri
,
Ali Vasheghani Farahani
Abstract
Background: Neuregulin-4 (Nrg4), a novel brown fat-enriched factor, has been reported to play a crucial role in developing metabolic disorders. The current case-control study aimed to investigate the association between serum Nrg4 and coronary artery disease (CAD).
Methods: This study enrolled 43 patients with CAD and 43 subjects with normal coronary arteries diagnosed by coronary angiography. Anthropometric and biochemical parameters were measured and recorded. The serum Nrg4 level was determined using the enzyme-linked immunosorbent assay. The relationships between circulating Nrg4 and CAD and other clinical parameters were analyzed. A receiver operating characteristic analysis was applied to assess the utility of Nrg4 in identifying CAD.
Results: The study population comprised 86 patients, including 64 men (74.4%), at a mean age of 57.83±6.01 years. Patients with CAD had significantly lower serum Nrg4 than the control group (P<0.001). The serum Nrg4 level was negatively correlated with anthropometric variables, including the body mass index, waist circumference, and the waist-to-hip ratio, fasting blood glucose, and the triglyceride-glucose index (P<0.05). In multivariable-adjusted regression analysis, the odds of CAD decreased by 46% per 1 SD elevation in the serum Nrg4 level (OR, 0.54; 95% CI, 0.40 to 0.73; P<0.001) after controlling for potential confounders. Nrg4 showed a significantly high area under the curve value (AUC, 0.85; 95% CI, 0.75 to 0.94) with 81.4% sensitivity and 95.3% specificity to identify CAD.
Conclusion: Generally, the serum level of Nrg4 declines in patients with CAD, which might be an independent risk factor for CAD.
1. Ralapanawa U, Sivakanesan R. Epidemiology and the Magnitude of Coronary Artery Disease and Acute Coronary Syndrome: A Narrative Review. J Epidemiol Glob Health 2021;11:169-177.
2. Rana MN, Neeland IJ. Adipose Tissue Inflammation and Cardiovascular Disease: An Update. Curr Diab Rep 2022;22:27-37.
3. Mack M, GoPal A. EPidemiology, traditional and novel risk factors in coronary artery disease. Heart Fail Clin 2016;12:1-10.
4. Juonala M, Magnussen CG, Berenson GS, Venn A, Burns TL, Sabin MA, Srinivasan SR, Daniels SR, Davis PH, Chen W, Sun C, Cheung M, Viikari JS, Dwyer T, Raitakari OT. Childhood adiposity, adult adiposity, and cardiovascular risk factors. N Engl J Med 2011;365:1876-185.
5. McGown C, Birerdinc A, Younossi ZM. Adipose tissue as an endocrine organ. Clin Liver Dis 2014;18:41-58.
6. Scheideler M, Herzig S, Georgiadi A. Endocrine and autocrine/paracrine modulators of brown adipose tissue mass and activity as novel therapeutic strategies against obesity and type 2 diabetes. Horm Mol Biol Clin Investig 2017;31:/j/hmbci.2017.31.issue-2/hmbci-2017-0043/hmbci-2017-0043.xml.
7. Blüher M, Mantzoros CS. From leptin to other adipokines in health and disease: facts and expectations at the beginning of the 21st century. Metabolism 2015 Jan;64:131-145.
8. Fasshauer M, Blüher M. Adipokines in health and disease. Trends Pharmacol Sci 2015;36:461-470.
9. Puchałowicz K, Kłoda K, Dziedziejko V, Rać M, Wojtarowicz A, Chlubek D, Safranow K. Association of Adiponectin, Leptin and Resistin Plasma Concentrations with Echocardiographic Parameters in Patients with Coronary Artery Disease. Diagnostics (Basel) 2021;11:1774.
10. Liu Y, Chen M. Neuregulin 4 as a novel adipokine in energy metabolism. Front Physiol 2023;13:1106380.
11. Harari D, Tzahar E, Romano J, Shelly M, Pierce JH, Andrews GC, Yarden Y. Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase. Oncogene 1999;18:2681-2689.
12. Christian M. Transcriptional fingerprinting of "browning" white fat identifies NRG4 as a novel adipokine. Adipocyte 2014;4:50-54.
13. Comas F, Martínez C, Sabater M, Ortega F, Latorre J, Díaz-Sáez F, Aragonés J, Camps M, Gumà A, Ricart W, Fernández-Real JM, Moreno-Navarrete JM. Neuregulin 4 Is a Novel Marker of Beige Adipocyte Precursor Cells in Human Adipose Tissue. Front Physiol 2019;10:39.
14. Tutunchi H, Ostadrahimi A, Hosseinzadeh-Attar MJ, Miryan M, Mobasseri M, Ebrahimi-Mameghani M. A systematic review of the association of neuregulin 4, a brown fat-enriched secreted factor, with obesity and related metabolic disturbances. Obes Rev 2020;21:e12952.
15. Dai YN, Zhu JZ, Fang ZY, Zhao DJ, Wan XY, Zhu HT, Yu CH, Li YM. A case-control study: Association between serum neuregulin 4 level and non-alcoholic fatty liver disease. Metabolism 2015;64:1667-1673.
16. Tutunchi H, Mobasseri M, Aghamohammadzadeh N, Hooshyar J, Naeini F, Najafipour F. Serum neuregulin 4 (NRG-4) level and non-alcoholic fatty liver disease (NAFLD): A case-control study. Int J Clin Pract 2021;75:e14555.
17. Cai C, Lin M, Xu Y, Li X, Yang S, Zhang H. Association of circulating neuregulin 4 with metabolic syndrome in obese adults: a cross-sectional study. BMC Med 2016;14:165.
18. Yan P, Xu Y, Zhang Z, Gao C, Zhu J, Li H, Wan Q. Decreased plasma neuregulin 4 levels are associated with peripheral neuropathy in Chinese patients with newly diagnosed type 2 diabetes: A cross-sectional study. Cytokine 2019;113:356-364.
19. Clement CM, Thomas LK, Mou Y, Croslan DR, Gibbons GH, Ford BD. Neuregulin-1 attenuates neointimal formation following vascular injury and inhibits the proliferation of vascular smooth muscle cells. J Vasc Res 2007;44:303-312.
20. Qin M, Luo Y, Meng XB, Wang M, Wang HW, Song SY, Ye JX, Pan RL, Yao F, Wu P, Sun GB, Sun XB. Myricitrin attenuates endothelial cell apoptosis to prevent atherosclerosis: An insight into PI3K/Akt activation and STAT3 signaling pathways. Vascul Pharmacol 2015;70:23-34.
21. Tie G, Yan J, Yang Y, Park BD, Messina JA, Raffai RL, Nowicki PT, Messina LM. Oxidized low-density lipoprotein induces apoptosis in endothelial progenitor cells by inactivating the phosphoinositide 3-kinase/Akt pathway. J Vasc Res 2010;47:519-530.
22. Jiang J, Lin M, Xu Y, Shao J, Li X, Zhang H, Yang S. Circulating neuregulin 4 levels are inversely associated with subclinical cardiovascular disease in obese adults. Sci Rep 2016;6:36710.
23. Tian QP, Liu ML, Tang CS, Xue L, Pang YZ, Qi YF. Association of Circulating Neuregulin-4 with Presence and Severity of Coronary Artery Disease. Int Heart J 2019;60:45-49.
24. Rahimzadeh M, Farshidi N, Naderi N, Farshidi H, Montazerghaem H. Clinical significance of serum concentrations of neuregulin-4, in acute coronary syndrome. Sci Rep 2020;10:5797.
25. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev 2004;84:277-359.
26. Lee P, Zhao JT, Swarbrick MM, Gracie G, Bova R, Greenfield JR, Freund J, Ho KK. High prevalence of brown adipose tissue in adult humans. J Clin Endocrinol Metab 2011;96:2450-2455.
27. Alcalá M, Calderon-Dominguez M, Serra D, Herrero L, Viana M. Mechanisms of Impaired Brown Adipose Tissue Recruitment in Obesity. Front Physiol 2019;10:94.
28. Yoneshiro T, Aita S, Matsushita M, Kayahara T, Kameya T, Kawai Y, Iwanaga T, Saito M. Recruited brown adipose tissue as an antiobesity agent in humans. J Clin Invest 2013;123:3404-3408.
29. Villarroya F, Cereijo R, Villarroya J, Giralt M. Brown adipose tissue as a secretory organ. Nat Rev Endocrinol 2017;13:26-35.
30. Rosell M, Kaforou M, Frontini A, Okolo A, Chan YW, Nikolopoulou E, Millership S, Fenech ME, MacIntyre D, Turner JO, Moore JD, Blackburn E, Gullick WJ, Cinti S, Montana G, Parker MG, Christian M. Brown and white adipose tissues: intrinsic differences in gene expression and response to cold exposure in mice. Am J Physiol Endocrinol Metab 2014;306:E945-964.
31. Pereira RO, McFarlane SI. The Role of Brown Adipose Tissue in Cardiovascular Disease Protection: Current Evidence and Future Directions. Int J Clin Res Trials 2019;4:136.
32. Bersell K, Arab S, Haring B, Kühn B. Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury Cell. 2009;138:257-270.
33. Iwamoto R, Yamazaki S, Asakura M, Takashima S, Hasuwa H, Miyado K, Adachi S, Kitakaze M, Hashimoto K, Raab G, Nanba D, Higashiyama S, Hori M, Klagsbrun M, Mekada E. Heparin-binding EGF-like growth factor and ErbB signaling is essential for heart function. Proc Natl Acad Sci U S A 2003;100:3221-3226.
34. Galindo CL, Ryzhov S, Sawyer DB. Neuregulin as a heart failure therapy and mediator of reverse remodeling. Curr Heart Fail Rep 2014;11:40-49.
35. Wang GX, Zhao XY, Meng ZX, Kern M, Dietrich A, Chen Z, Cozacov Z, Zhou D, Okunade AL, Su X, Li S, Blüher M, Lin JD. The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis. Nat Med 2014;20:1436-1443.
36. Wang R, Yang F, Qing L, Huang R, Liu Q, Li X. Decreased serum neuregulin 4 levels associated with non-alcoholic fatty liver disease in children with obesity. Clin Obes 2019;9:e12289.
37. Chen Z, Wang GX, Ma SL, Jung DY, Ha H, Altamimi T, Zhao XY, Guo L, Zhang P, Hu CR, Cheng JX, Lopaschuk GD, Kim JK, Lin JD. Nrg4 promotes fuel oxidation and a healthy adipokine profile to ameliorate diet-induced metabolic disorders. Mol Metab 2017;6:863-872.
38. Ma Y, Gao M, Liu D. Preventing High Fat Diet-induced Obesity and Improving Insulin Sensitivity through Neuregulin 4 Gene Transfer. Sci Rep 2016;6:26242.
39. Zhang L, Fu Y, Zhou N, Cheng X, Chen C. Circulating neuregulin 4 concentrations in patients with newly diagnosed type 2 diabetes: a cross-sectional study. Endocrine 2017;57:535-538.
40. Kralisch S, Hoffmann A, Kratzsch J, Blüher M, Stumvoll M, Fasshauer M, Ebert T. The brown-fat-secreted adipokine neuregulin 4 is decreased in gestational diabetes mellitus. Diabetes Metab 2018;44:150-154..
41. Guo L, Zhang P, Chen Z, Xia H, Li S, Zhang Y, Kobberup S, Zou W, Lin JD. Hepatic neuregulin 4 signaling defines an endocrine checkpoint for steatosis-to-NASH progression. J Clin Invest 2017;127:4449-4461.
42. Bernard JK, McCann SP, Bhardwaj V, Washington MK, Frey MR. Neuregulin-4 is a survival factor for colon epithelial cells both in culture and in vivo. J Biol Chem 2012;287:39850-39858.
43. Chen LL, Peng MM, Zhang JY, Hu X, Min J, Huang QL, Wan LM. Elevated circulating Neuregulin4 level in patients with diabetes. Diabetes Metab Res Rev 2017;33.
44. Shi L, Xu X, Meng B, He K, Sun Y, Tong J, Xu J, Cheng Y, Gan G, Xiang G. Neuregulin 4 Attenuates Osteoarthritis Progression by Inhibiting Inflammation and Apoptosis of Chondrocytes in Mice. Calcif Tissue Int 2022;110:131-142.
45. Schumacher MA, Hedl M, Abraham C, Bernard JK, Lozano PR, Hsieh JJ, Almohazey D, Bucar EB, Punit S, Dempsey PJ, Frey MR. ErbB4 signaling stimulates pro-inflammatory macrophage apoptosis and limits colonic inflammation. Cell Death Dis 2017;8:e2622.
46. Stoll G, Bendszus M. Inflammation and atherosclerosis: novel insights into plaque formation and destabilization. Stroke 2006;37:1923-1932.
47. Zhong M, Tian X, Sun Q, Li L, Lu Y, Feng Z, Gao Y, Li S. Correlation of asprosin and Nrg-4 with type 2 diabetes Mellitus Complicated with Coronary Heart Disease and the Diagnostic Value. BMC Endocr Disord 2023;23:61.
2. Rana MN, Neeland IJ. Adipose Tissue Inflammation and Cardiovascular Disease: An Update. Curr Diab Rep 2022;22:27-37.
3. Mack M, GoPal A. EPidemiology, traditional and novel risk factors in coronary artery disease. Heart Fail Clin 2016;12:1-10.
4. Juonala M, Magnussen CG, Berenson GS, Venn A, Burns TL, Sabin MA, Srinivasan SR, Daniels SR, Davis PH, Chen W, Sun C, Cheung M, Viikari JS, Dwyer T, Raitakari OT. Childhood adiposity, adult adiposity, and cardiovascular risk factors. N Engl J Med 2011;365:1876-185.
5. McGown C, Birerdinc A, Younossi ZM. Adipose tissue as an endocrine organ. Clin Liver Dis 2014;18:41-58.
6. Scheideler M, Herzig S, Georgiadi A. Endocrine and autocrine/paracrine modulators of brown adipose tissue mass and activity as novel therapeutic strategies against obesity and type 2 diabetes. Horm Mol Biol Clin Investig 2017;31:/j/hmbci.2017.31.issue-2/hmbci-2017-0043/hmbci-2017-0043.xml.
7. Blüher M, Mantzoros CS. From leptin to other adipokines in health and disease: facts and expectations at the beginning of the 21st century. Metabolism 2015 Jan;64:131-145.
8. Fasshauer M, Blüher M. Adipokines in health and disease. Trends Pharmacol Sci 2015;36:461-470.
9. Puchałowicz K, Kłoda K, Dziedziejko V, Rać M, Wojtarowicz A, Chlubek D, Safranow K. Association of Adiponectin, Leptin and Resistin Plasma Concentrations with Echocardiographic Parameters in Patients with Coronary Artery Disease. Diagnostics (Basel) 2021;11:1774.
10. Liu Y, Chen M. Neuregulin 4 as a novel adipokine in energy metabolism. Front Physiol 2023;13:1106380.
11. Harari D, Tzahar E, Romano J, Shelly M, Pierce JH, Andrews GC, Yarden Y. Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase. Oncogene 1999;18:2681-2689.
12. Christian M. Transcriptional fingerprinting of "browning" white fat identifies NRG4 as a novel adipokine. Adipocyte 2014;4:50-54.
13. Comas F, Martínez C, Sabater M, Ortega F, Latorre J, Díaz-Sáez F, Aragonés J, Camps M, Gumà A, Ricart W, Fernández-Real JM, Moreno-Navarrete JM. Neuregulin 4 Is a Novel Marker of Beige Adipocyte Precursor Cells in Human Adipose Tissue. Front Physiol 2019;10:39.
14. Tutunchi H, Ostadrahimi A, Hosseinzadeh-Attar MJ, Miryan M, Mobasseri M, Ebrahimi-Mameghani M. A systematic review of the association of neuregulin 4, a brown fat-enriched secreted factor, with obesity and related metabolic disturbances. Obes Rev 2020;21:e12952.
15. Dai YN, Zhu JZ, Fang ZY, Zhao DJ, Wan XY, Zhu HT, Yu CH, Li YM. A case-control study: Association between serum neuregulin 4 level and non-alcoholic fatty liver disease. Metabolism 2015;64:1667-1673.
16. Tutunchi H, Mobasseri M, Aghamohammadzadeh N, Hooshyar J, Naeini F, Najafipour F. Serum neuregulin 4 (NRG-4) level and non-alcoholic fatty liver disease (NAFLD): A case-control study. Int J Clin Pract 2021;75:e14555.
17. Cai C, Lin M, Xu Y, Li X, Yang S, Zhang H. Association of circulating neuregulin 4 with metabolic syndrome in obese adults: a cross-sectional study. BMC Med 2016;14:165.
18. Yan P, Xu Y, Zhang Z, Gao C, Zhu J, Li H, Wan Q. Decreased plasma neuregulin 4 levels are associated with peripheral neuropathy in Chinese patients with newly diagnosed type 2 diabetes: A cross-sectional study. Cytokine 2019;113:356-364.
19. Clement CM, Thomas LK, Mou Y, Croslan DR, Gibbons GH, Ford BD. Neuregulin-1 attenuates neointimal formation following vascular injury and inhibits the proliferation of vascular smooth muscle cells. J Vasc Res 2007;44:303-312.
20. Qin M, Luo Y, Meng XB, Wang M, Wang HW, Song SY, Ye JX, Pan RL, Yao F, Wu P, Sun GB, Sun XB. Myricitrin attenuates endothelial cell apoptosis to prevent atherosclerosis: An insight into PI3K/Akt activation and STAT3 signaling pathways. Vascul Pharmacol 2015;70:23-34.
21. Tie G, Yan J, Yang Y, Park BD, Messina JA, Raffai RL, Nowicki PT, Messina LM. Oxidized low-density lipoprotein induces apoptosis in endothelial progenitor cells by inactivating the phosphoinositide 3-kinase/Akt pathway. J Vasc Res 2010;47:519-530.
22. Jiang J, Lin M, Xu Y, Shao J, Li X, Zhang H, Yang S. Circulating neuregulin 4 levels are inversely associated with subclinical cardiovascular disease in obese adults. Sci Rep 2016;6:36710.
23. Tian QP, Liu ML, Tang CS, Xue L, Pang YZ, Qi YF. Association of Circulating Neuregulin-4 with Presence and Severity of Coronary Artery Disease. Int Heart J 2019;60:45-49.
24. Rahimzadeh M, Farshidi N, Naderi N, Farshidi H, Montazerghaem H. Clinical significance of serum concentrations of neuregulin-4, in acute coronary syndrome. Sci Rep 2020;10:5797.
25. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev 2004;84:277-359.
26. Lee P, Zhao JT, Swarbrick MM, Gracie G, Bova R, Greenfield JR, Freund J, Ho KK. High prevalence of brown adipose tissue in adult humans. J Clin Endocrinol Metab 2011;96:2450-2455.
27. Alcalá M, Calderon-Dominguez M, Serra D, Herrero L, Viana M. Mechanisms of Impaired Brown Adipose Tissue Recruitment in Obesity. Front Physiol 2019;10:94.
28. Yoneshiro T, Aita S, Matsushita M, Kayahara T, Kameya T, Kawai Y, Iwanaga T, Saito M. Recruited brown adipose tissue as an antiobesity agent in humans. J Clin Invest 2013;123:3404-3408.
29. Villarroya F, Cereijo R, Villarroya J, Giralt M. Brown adipose tissue as a secretory organ. Nat Rev Endocrinol 2017;13:26-35.
30. Rosell M, Kaforou M, Frontini A, Okolo A, Chan YW, Nikolopoulou E, Millership S, Fenech ME, MacIntyre D, Turner JO, Moore JD, Blackburn E, Gullick WJ, Cinti S, Montana G, Parker MG, Christian M. Brown and white adipose tissues: intrinsic differences in gene expression and response to cold exposure in mice. Am J Physiol Endocrinol Metab 2014;306:E945-964.
31. Pereira RO, McFarlane SI. The Role of Brown Adipose Tissue in Cardiovascular Disease Protection: Current Evidence and Future Directions. Int J Clin Res Trials 2019;4:136.
32. Bersell K, Arab S, Haring B, Kühn B. Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury Cell. 2009;138:257-270.
33. Iwamoto R, Yamazaki S, Asakura M, Takashima S, Hasuwa H, Miyado K, Adachi S, Kitakaze M, Hashimoto K, Raab G, Nanba D, Higashiyama S, Hori M, Klagsbrun M, Mekada E. Heparin-binding EGF-like growth factor and ErbB signaling is essential for heart function. Proc Natl Acad Sci U S A 2003;100:3221-3226.
34. Galindo CL, Ryzhov S, Sawyer DB. Neuregulin as a heart failure therapy and mediator of reverse remodeling. Curr Heart Fail Rep 2014;11:40-49.
35. Wang GX, Zhao XY, Meng ZX, Kern M, Dietrich A, Chen Z, Cozacov Z, Zhou D, Okunade AL, Su X, Li S, Blüher M, Lin JD. The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis. Nat Med 2014;20:1436-1443.
36. Wang R, Yang F, Qing L, Huang R, Liu Q, Li X. Decreased serum neuregulin 4 levels associated with non-alcoholic fatty liver disease in children with obesity. Clin Obes 2019;9:e12289.
37. Chen Z, Wang GX, Ma SL, Jung DY, Ha H, Altamimi T, Zhao XY, Guo L, Zhang P, Hu CR, Cheng JX, Lopaschuk GD, Kim JK, Lin JD. Nrg4 promotes fuel oxidation and a healthy adipokine profile to ameliorate diet-induced metabolic disorders. Mol Metab 2017;6:863-872.
38. Ma Y, Gao M, Liu D. Preventing High Fat Diet-induced Obesity and Improving Insulin Sensitivity through Neuregulin 4 Gene Transfer. Sci Rep 2016;6:26242.
39. Zhang L, Fu Y, Zhou N, Cheng X, Chen C. Circulating neuregulin 4 concentrations in patients with newly diagnosed type 2 diabetes: a cross-sectional study. Endocrine 2017;57:535-538.
40. Kralisch S, Hoffmann A, Kratzsch J, Blüher M, Stumvoll M, Fasshauer M, Ebert T. The brown-fat-secreted adipokine neuregulin 4 is decreased in gestational diabetes mellitus. Diabetes Metab 2018;44:150-154..
41. Guo L, Zhang P, Chen Z, Xia H, Li S, Zhang Y, Kobberup S, Zou W, Lin JD. Hepatic neuregulin 4 signaling defines an endocrine checkpoint for steatosis-to-NASH progression. J Clin Invest 2017;127:4449-4461.
42. Bernard JK, McCann SP, Bhardwaj V, Washington MK, Frey MR. Neuregulin-4 is a survival factor for colon epithelial cells both in culture and in vivo. J Biol Chem 2012;287:39850-39858.
43. Chen LL, Peng MM, Zhang JY, Hu X, Min J, Huang QL, Wan LM. Elevated circulating Neuregulin4 level in patients with diabetes. Diabetes Metab Res Rev 2017;33.
44. Shi L, Xu X, Meng B, He K, Sun Y, Tong J, Xu J, Cheng Y, Gan G, Xiang G. Neuregulin 4 Attenuates Osteoarthritis Progression by Inhibiting Inflammation and Apoptosis of Chondrocytes in Mice. Calcif Tissue Int 2022;110:131-142.
45. Schumacher MA, Hedl M, Abraham C, Bernard JK, Lozano PR, Hsieh JJ, Almohazey D, Bucar EB, Punit S, Dempsey PJ, Frey MR. ErbB4 signaling stimulates pro-inflammatory macrophage apoptosis and limits colonic inflammation. Cell Death Dis 2017;8:e2622.
46. Stoll G, Bendszus M. Inflammation and atherosclerosis: novel insights into plaque formation and destabilization. Stroke 2006;37:1923-1932.
47. Zhong M, Tian X, Sun Q, Li L, Lu Y, Feng Z, Gao Y, Li S. Correlation of asprosin and Nrg-4 with type 2 diabetes Mellitus Complicated with Coronary Heart Disease and the Diagnostic Value. BMC Endocr Disord 2023;23:61.
| Files | ||
| Issue | Vol 18 No 3 (2023): J Teh Univ Heart Ctr | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/jthc.v18i3.14111 | |
| Keywords | ||
| Coronary artery disease Neuregulin-4 Adipokines | ||
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How to Cite
1.
Taheri F, Hosseinzadeh-Attar MJ, Alipoor E, Honarkar-Shafie E, Yaseri M, Vasheghani Farahani A. Implications of the Serum Concentrations of Neuregulin-4 (Nrg4) in Patients with Coronary Artery Disease: A Case-Control Study. J Tehran Heart Cent. 2023;18(3):170-176.
