Main Article Content
Abstract
Familial hypercholesterolemia (FH) is an autosomal dominant lipid metabolic condition that affects people from birth. Low-density lipoprotein cholesterol (LDL-C) levels are extremely high. Patients with familial hypercholesterolemia and hypercholesterolemia have a nearly two-fold increased risk of developing cardiovascular disease (CVD). LRP-1 serves as a scavenger receptor, a regulatory receptor, and a scaffold receptor. A total of 150 blood samples were taken from people, with 50 of them being patients with familial hypercholesterolemia, non-familial hypercholesterolemia, and healthy control subjects. This study aimed to measure gene expression for LRP-1 gene and mir-205 and indicating their relationship to the development of cardiovascular disease in familial hypercholesterolemia and non-familial hypercholesterolemia. Also, screening for familial hypercholesterolemia and its connection cardiovascular disease using mir-205 as a biomarker specific and sensitive for the LRP-1 gene was done. The expression of LRP-1 and mir-205 in whole blood was estimated using reverse transcriptase quantitative real time polymerase chain reaction. The results showed that the expression of LRP-1 in the fold of gene expression in F.H patients' group was lower than that of healthy group, while the expression of mir-205 in the fold of gene expression in F.H patients' group was 14 time higher than that of healthy group. The results also showed low LRP-1 expression is present in familial hypercholesterolemia and non-familial hypercholesterolemia. The familial hypercholesterolemia group was associated with the lowest expression of LRP-1 and followed by the non-familial hypercholesterolemia. This reflects an increased susceptibility to cardiovascular disease. overexpression of mir-205 is found in familial hypercholesterolemia and non-familial hypercholesterolemia. The familial hypercholesterolemia group was associated with the highest expression of mir-205 and followed by the non-familial hypercholesterolemia. This reflects that mir-205 is overexpressed in the cardiovascular system, suppressing LRP1 translation and thereby lowering LRP1 protein levels.
Keywords
Hypercholesterolemia
LRP-1 gene
Mir-205
Gene expression
RT-PCR.
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The authors transfer the copyrights of their papers to the Iranian Society of Ichthyology. However, the information could be used in accordance with the Creative Commons licence (Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
How to Cite
GHAREEB, Z. A., AL-KHAFAJI, H. M. A.-H., & AL-SAEDI, M. K. A. (2021). Low-density lipoprotein receptor-related protein-1 and mir-205 expression for cardiovascular disease in familial hypercholesterolemia and non-familial hypercholesterolemia in Iraqi population. Iranian Journal of Ichthyology, 8, 246–254. Retrieved from https://ijichthyol.org/index.php/iji/article/view/690
References
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Abed, S.A. & Al-Khafaji, H.M. 2021. Design of primer and probe to detect SNP Rs 1892901 in Fosl-1Gene in different types of cancer in Iraqi population. Systematic Reviews in Pharmacy 12(1): 296-300.
Al-Khafaji, H.M. 2017. Gene Expression Bcl-2 Gene in Cancer of Brest in Iraqi population. Engineering and Technology Journal 35(2 Part B): 119-125.
Bandyopadhyay, D.; Qureshi, A.; Ghosh, S.; Ashish, K.; Heise, L.R. Hajra, A. & Ghosh, R.K. 2018. Safety and efficacy of extremely low LDL-cholesterol levels and its prospects in hyperlipidemia management. Journal of Lipids 2018.
Chan, C.Y.T.; Chan, Y.C.; Cheuk, B.L.Y. & Cheng, S.W.K. 2017. Clearance of matrix metalloproteinase-9 is dependent on low-density lipoprotein receptor-related protein-1 expression downregulated by microRNA-205 in human abdominal aortic aneurysm. Journal of Vascular Surgery 65(2): 509-520.
Cruz-Bautista, I., Mehta, R., Cabiedes, J., García-Ulloa, C., Guillen-Pineda, L.E., Almeda-Valdés, P. & Aguilar-Salinas, C.A. 2015. Determinants of VLDL composition and apo B-containing particles in familial combined hyperlipidemia. Clinica Chimica Acta 438: 160-165.
Do, R.; Stitziel, N.O.; Won, H.H.; Jørgensen, A.B.; Duga, S.; Merlini, P.A. & Kathiresan, S. 2015. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature 518(7537): 102-106.
Feng, L.; Wei, J.; Liang, S.; Sun, Z. & Duan, J. 2020. miR-205/IRAK2 signaling pathway is associated with urban airborne PM2. 5-induced myocardial toxicity. Nanotoxicology 14(9): 1198-1212.
Gorovoy, M.; Gaultier, A.; Campana, W.M.; Firestein, G.S. & Gonias, S.L. 2010. Inflammatory mediators promote production of shed LRP1/CD91, which regulates cell signaling and cytokine expression by macrophages. Journal of Leukocyte Biology 88(4): 769-778.
Haque, A.T.; Yusoff, F.B.; Ariffin, M.H.; Hamid, M.F. Hashim, S.R.B. & Haque, M. 2016. Lipid profile of the coronary heart disease (CHD) patients admitted in a Hospital in Malaysia. Journal of Applied Pharmaceutical Science 6(5): 137-142.
Kim, C.W.; Kumar, S.; Son, D.J.; Jang, I.H., Griendling, K.K. & Jo, H. 2014. Prevention of abdominal aortic aneurysm by Anti–MicroRNA-712 or Anti–MicroRNA-205 in angiotensin II–infused mice. Arteriosclerosis, Thrombosis, and Vascular Biology 34(7): 1412-1421.
Klar, J.; Schuster, J.; Khan, T.N.; Jameel, M.; Mäbert, K.; Forsberg, L. & Dahl, N. 2015. Whole exome sequencing identifies LRP1 as a pathogenic gene in autosomal recessive keratosis Pilaris atrophicans. Journal of Medical Genetics 52(9): 599-606.
Lee, S.; Akioyamen, L.E.; Aljenedil, S.; Rivière, J. B.; Ruel, I. & Genest, J. 2019. Genetic testing for familial hypercholesterolemia: impact on diagnosis, treatment and cardiovascular risk. European Journal of Preventive Cardiology 26(12): 1262-1270.
Lillis, A.P.; Greenlee, M.C.; Mikhailenko, I.; Pizzo, S.V.; Tenner, A.J.; Strickland, D.K. & Bohlson, S.S. 2008. Murine low-density lipoprotein receptor-related protein 1 (LRP) is required for phagocytosis of targets bearing LRP ligands but is not required for C1q-triggered enhancement of phagocytosis. The Journal of Immunology 181(1): 364-373.
Lim, L.P.; Glasner, M.E.; Yekta, S.; Burge, C.B. & Bartel, D.P. 2003. Vertebrate microRNA genes. Science 299(5612): 1540-1540.
Lin, Y.C.; Chang, N.T.; Chuang, S.Y. & Su, T.C. 2019. Relationship of the Association between Sarcopenia and Cardiovascular Risk in Patient of Familial Hyperlipidemia. Journal of Obesity and Metabolic Syndrome 1(2S): 58-58.
Marrone, A.K.; Beland, F.A. & Pogribny, I.P. 2015. The role for microRNAs in drug toxicity and in safety assessment. Expert Opinion on Drug Metabolism & Toxicology 11(4): 601-611.
Mashali, H.; Toleideh, F.; Rahmani, R.; Darabiyan, P. & Madmoli, M. 2018. The predictive role of Hyperlipidemia in the incidence of ACS in patients referring to Shahidzadeh Hospital in Behbahan in 2016-2017. Medical Science 22(94): 566-570.
Najam, O. & Ray, K.K. 2015. Familial hypercholesterolemia: a review of the natural history, diagnosis, and management. Cardiology and Therapy 4(1): 25-38.
Obaid, S.N. & AL-Saadi, B.Q. 2018. Study the effects of STRA 6 gene polymorphism on the incidence of T2DM in a sample of Iraqi patients. Iraqi Journal of Biotechnology 17(1): 1-5.
Potere, N.; Del Buono, M.G.; Mauro, A.G.; Abbate, A. & Toldo, S. 2019. Low density lipoprotein receptor-related protein-1 in cardiac inflammation and infarct healing. Frontiers in Cardiovascular Medicine 6, 51.
Qin, A.Y.; Zhang, X.W.; Liu, L.; Yu, J.P.; Li, H.; Wang, S.Z.E. & Cao, S. 2013. MiR-205 in cancer: an angel or a devil? European Journal of Cell Biology 92(2): 54-60.
Soro, A.; Jauhiainen, M.; Ehnholm, C. & Taskinen, M.R. 2003. Determinants of low HDL levels in familial combined hyperlipidemia. Journal of Lipid Research 44(8): 1536-1544.
Srivastava, R.A.K. 2018. Dysfunctional HDL in diabetes mellitus and its role in the pathogenesis of cardiovascular disease. Molecular and Cellular Biochemistry 440(1): 167-187.
Van De Sluis, B.; Wijers, M. & Herz, J.2017. News on the molecular regulation and function of hepatic LDLR and LRP1. Current Opinion in Lipidology 28(3): 241.
Wieczorek, E.; Ćwiklińska, A.; Kuchta, A.; Kortas-Stempak, B.; Gliwińska, A. & Jankowski, M. 2021. Decreased Efficiency of Very-Low-Density Lipoprotein Lipolysis Is Linked to Both Hypertriglyceridemia and Hypercholesterolemia, but It Can Be Counteracted by High-Density Lipoprotein. Nutrients 13(4): 1224.
Wong, B.; Kruse, G.; Kutikova, L.; Ray, K.K.; Mata, P. & Bruckert, E. 2016. Cardiovascular disease risk associated with familial hypercholesterolemia: a systematic review of the literature. Clinical Therapeutics 38(7): 1696-1709.
Xu, Y. & Fu, M. 2003. Alterations of HDL subclasses in hyperlipidemia. Clinica Chimica Acta 332(1-2): 95-102.
Xuan, Y.; Liu, S.; Li, Y.; Dong, J.; Luo, J.; Liu, T. & Sun, Z. 2017. Short term vagus nerve stimulation reduces myocardial apoptosis by downregulating microRNA 205 in rats with chronic heart failure. Molecular Medicine Reports 16(5): 5847-5854.
References
Abed, S.A. & Al-Khafaji, H.M. 2021. Design of primer and probe to detect SNP Rs 1892901 in Fosl-1Gene in different types of cancer in Iraqi population. Systematic Reviews in Pharmacy 12(1): 296-300.
Al-Khafaji, H.M. 2017. Gene Expression Bcl-2 Gene in Cancer of Brest in Iraqi population. Engineering and Technology Journal 35(2 Part B): 119-125.
Bandyopadhyay, D.; Qureshi, A.; Ghosh, S.; Ashish, K.; Heise, L.R. Hajra, A. & Ghosh, R.K. 2018. Safety and efficacy of extremely low LDL-cholesterol levels and its prospects in hyperlipidemia management. Journal of Lipids 2018.
Chan, C.Y.T.; Chan, Y.C.; Cheuk, B.L.Y. & Cheng, S.W.K. 2017. Clearance of matrix metalloproteinase-9 is dependent on low-density lipoprotein receptor-related protein-1 expression downregulated by microRNA-205 in human abdominal aortic aneurysm. Journal of Vascular Surgery 65(2): 509-520.
Cruz-Bautista, I., Mehta, R., Cabiedes, J., García-Ulloa, C., Guillen-Pineda, L.E., Almeda-Valdés, P. & Aguilar-Salinas, C.A. 2015. Determinants of VLDL composition and apo B-containing particles in familial combined hyperlipidemia. Clinica Chimica Acta 438: 160-165.
Do, R.; Stitziel, N.O.; Won, H.H.; Jørgensen, A.B.; Duga, S.; Merlini, P.A. & Kathiresan, S. 2015. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature 518(7537): 102-106.
Feng, L.; Wei, J.; Liang, S.; Sun, Z. & Duan, J. 2020. miR-205/IRAK2 signaling pathway is associated with urban airborne PM2. 5-induced myocardial toxicity. Nanotoxicology 14(9): 1198-1212.
Gorovoy, M.; Gaultier, A.; Campana, W.M.; Firestein, G.S. & Gonias, S.L. 2010. Inflammatory mediators promote production of shed LRP1/CD91, which regulates cell signaling and cytokine expression by macrophages. Journal of Leukocyte Biology 88(4): 769-778.
Haque, A.T.; Yusoff, F.B.; Ariffin, M.H.; Hamid, M.F. Hashim, S.R.B. & Haque, M. 2016. Lipid profile of the coronary heart disease (CHD) patients admitted in a Hospital in Malaysia. Journal of Applied Pharmaceutical Science 6(5): 137-142.
Kim, C.W.; Kumar, S.; Son, D.J.; Jang, I.H., Griendling, K.K. & Jo, H. 2014. Prevention of abdominal aortic aneurysm by Anti–MicroRNA-712 or Anti–MicroRNA-205 in angiotensin II–infused mice. Arteriosclerosis, Thrombosis, and Vascular Biology 34(7): 1412-1421.
Klar, J.; Schuster, J.; Khan, T.N.; Jameel, M.; Mäbert, K.; Forsberg, L. & Dahl, N. 2015. Whole exome sequencing identifies LRP1 as a pathogenic gene in autosomal recessive keratosis Pilaris atrophicans. Journal of Medical Genetics 52(9): 599-606.
Lee, S.; Akioyamen, L.E.; Aljenedil, S.; Rivière, J. B.; Ruel, I. & Genest, J. 2019. Genetic testing for familial hypercholesterolemia: impact on diagnosis, treatment and cardiovascular risk. European Journal of Preventive Cardiology 26(12): 1262-1270.
Lillis, A.P.; Greenlee, M.C.; Mikhailenko, I.; Pizzo, S.V.; Tenner, A.J.; Strickland, D.K. & Bohlson, S.S. 2008. Murine low-density lipoprotein receptor-related protein 1 (LRP) is required for phagocytosis of targets bearing LRP ligands but is not required for C1q-triggered enhancement of phagocytosis. The Journal of Immunology 181(1): 364-373.
Lim, L.P.; Glasner, M.E.; Yekta, S.; Burge, C.B. & Bartel, D.P. 2003. Vertebrate microRNA genes. Science 299(5612): 1540-1540.
Lin, Y.C.; Chang, N.T.; Chuang, S.Y. & Su, T.C. 2019. Relationship of the Association between Sarcopenia and Cardiovascular Risk in Patient of Familial Hyperlipidemia. Journal of Obesity and Metabolic Syndrome 1(2S): 58-58.
Marrone, A.K.; Beland, F.A. & Pogribny, I.P. 2015. The role for microRNAs in drug toxicity and in safety assessment. Expert Opinion on Drug Metabolism & Toxicology 11(4): 601-611.
Mashali, H.; Toleideh, F.; Rahmani, R.; Darabiyan, P. & Madmoli, M. 2018. The predictive role of Hyperlipidemia in the incidence of ACS in patients referring to Shahidzadeh Hospital in Behbahan in 2016-2017. Medical Science 22(94): 566-570.
Najam, O. & Ray, K.K. 2015. Familial hypercholesterolemia: a review of the natural history, diagnosis, and management. Cardiology and Therapy 4(1): 25-38.
Obaid, S.N. & AL-Saadi, B.Q. 2018. Study the effects of STRA 6 gene polymorphism on the incidence of T2DM in a sample of Iraqi patients. Iraqi Journal of Biotechnology 17(1): 1-5.
Potere, N.; Del Buono, M.G.; Mauro, A.G.; Abbate, A. & Toldo, S. 2019. Low density lipoprotein receptor-related protein-1 in cardiac inflammation and infarct healing. Frontiers in Cardiovascular Medicine 6, 51.
Qin, A.Y.; Zhang, X.W.; Liu, L.; Yu, J.P.; Li, H.; Wang, S.Z.E. & Cao, S. 2013. MiR-205 in cancer: an angel or a devil? European Journal of Cell Biology 92(2): 54-60.
Soro, A.; Jauhiainen, M.; Ehnholm, C. & Taskinen, M.R. 2003. Determinants of low HDL levels in familial combined hyperlipidemia. Journal of Lipid Research 44(8): 1536-1544.
Srivastava, R.A.K. 2018. Dysfunctional HDL in diabetes mellitus and its role in the pathogenesis of cardiovascular disease. Molecular and Cellular Biochemistry 440(1): 167-187.
Van De Sluis, B.; Wijers, M. & Herz, J.2017. News on the molecular regulation and function of hepatic LDLR and LRP1. Current Opinion in Lipidology 28(3): 241.
Wieczorek, E.; Ćwiklińska, A.; Kuchta, A.; Kortas-Stempak, B.; Gliwińska, A. & Jankowski, M. 2021. Decreased Efficiency of Very-Low-Density Lipoprotein Lipolysis Is Linked to Both Hypertriglyceridemia and Hypercholesterolemia, but It Can Be Counteracted by High-Density Lipoprotein. Nutrients 13(4): 1224.
Wong, B.; Kruse, G.; Kutikova, L.; Ray, K.K.; Mata, P. & Bruckert, E. 2016. Cardiovascular disease risk associated with familial hypercholesterolemia: a systematic review of the literature. Clinical Therapeutics 38(7): 1696-1709.
Xu, Y. & Fu, M. 2003. Alterations of HDL subclasses in hyperlipidemia. Clinica Chimica Acta 332(1-2): 95-102.
Xuan, Y.; Liu, S.; Li, Y.; Dong, J.; Luo, J.; Liu, T. & Sun, Z. 2017. Short term vagus nerve stimulation reduces myocardial apoptosis by downregulating microRNA 205 in rats with chronic heart failure. Molecular Medicine Reports 16(5): 5847-5854.
Al-Khafaji, H.M. 2017. Gene Expression Bcl-2 Gene in Cancer of Brest in Iraqi population. Engineering and Technology Journal 35(2 Part B): 119-125.
Bandyopadhyay, D.; Qureshi, A.; Ghosh, S.; Ashish, K.; Heise, L.R. Hajra, A. & Ghosh, R.K. 2018. Safety and efficacy of extremely low LDL-cholesterol levels and its prospects in hyperlipidemia management. Journal of Lipids 2018.
Chan, C.Y.T.; Chan, Y.C.; Cheuk, B.L.Y. & Cheng, S.W.K. 2017. Clearance of matrix metalloproteinase-9 is dependent on low-density lipoprotein receptor-related protein-1 expression downregulated by microRNA-205 in human abdominal aortic aneurysm. Journal of Vascular Surgery 65(2): 509-520.
Cruz-Bautista, I., Mehta, R., Cabiedes, J., García-Ulloa, C., Guillen-Pineda, L.E., Almeda-Valdés, P. & Aguilar-Salinas, C.A. 2015. Determinants of VLDL composition and apo B-containing particles in familial combined hyperlipidemia. Clinica Chimica Acta 438: 160-165.
Do, R.; Stitziel, N.O.; Won, H.H.; Jørgensen, A.B.; Duga, S.; Merlini, P.A. & Kathiresan, S. 2015. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature 518(7537): 102-106.
Feng, L.; Wei, J.; Liang, S.; Sun, Z. & Duan, J. 2020. miR-205/IRAK2 signaling pathway is associated with urban airborne PM2. 5-induced myocardial toxicity. Nanotoxicology 14(9): 1198-1212.
Gorovoy, M.; Gaultier, A.; Campana, W.M.; Firestein, G.S. & Gonias, S.L. 2010. Inflammatory mediators promote production of shed LRP1/CD91, which regulates cell signaling and cytokine expression by macrophages. Journal of Leukocyte Biology 88(4): 769-778.
Haque, A.T.; Yusoff, F.B.; Ariffin, M.H.; Hamid, M.F. Hashim, S.R.B. & Haque, M. 2016. Lipid profile of the coronary heart disease (CHD) patients admitted in a Hospital in Malaysia. Journal of Applied Pharmaceutical Science 6(5): 137-142.
Kim, C.W.; Kumar, S.; Son, D.J.; Jang, I.H., Griendling, K.K. & Jo, H. 2014. Prevention of abdominal aortic aneurysm by Anti–MicroRNA-712 or Anti–MicroRNA-205 in angiotensin II–infused mice. Arteriosclerosis, Thrombosis, and Vascular Biology 34(7): 1412-1421.
Klar, J.; Schuster, J.; Khan, T.N.; Jameel, M.; Mäbert, K.; Forsberg, L. & Dahl, N. 2015. Whole exome sequencing identifies LRP1 as a pathogenic gene in autosomal recessive keratosis Pilaris atrophicans. Journal of Medical Genetics 52(9): 599-606.
Lee, S.; Akioyamen, L.E.; Aljenedil, S.; Rivière, J. B.; Ruel, I. & Genest, J. 2019. Genetic testing for familial hypercholesterolemia: impact on diagnosis, treatment and cardiovascular risk. European Journal of Preventive Cardiology 26(12): 1262-1270.
Lillis, A.P.; Greenlee, M.C.; Mikhailenko, I.; Pizzo, S.V.; Tenner, A.J.; Strickland, D.K. & Bohlson, S.S. 2008. Murine low-density lipoprotein receptor-related protein 1 (LRP) is required for phagocytosis of targets bearing LRP ligands but is not required for C1q-triggered enhancement of phagocytosis. The Journal of Immunology 181(1): 364-373.
Lim, L.P.; Glasner, M.E.; Yekta, S.; Burge, C.B. & Bartel, D.P. 2003. Vertebrate microRNA genes. Science 299(5612): 1540-1540.
Lin, Y.C.; Chang, N.T.; Chuang, S.Y. & Su, T.C. 2019. Relationship of the Association between Sarcopenia and Cardiovascular Risk in Patient of Familial Hyperlipidemia. Journal of Obesity and Metabolic Syndrome 1(2S): 58-58.
Marrone, A.K.; Beland, F.A. & Pogribny, I.P. 2015. The role for microRNAs in drug toxicity and in safety assessment. Expert Opinion on Drug Metabolism & Toxicology 11(4): 601-611.
Mashali, H.; Toleideh, F.; Rahmani, R.; Darabiyan, P. & Madmoli, M. 2018. The predictive role of Hyperlipidemia in the incidence of ACS in patients referring to Shahidzadeh Hospital in Behbahan in 2016-2017. Medical Science 22(94): 566-570.
Najam, O. & Ray, K.K. 2015. Familial hypercholesterolemia: a review of the natural history, diagnosis, and management. Cardiology and Therapy 4(1): 25-38.
Obaid, S.N. & AL-Saadi, B.Q. 2018. Study the effects of STRA 6 gene polymorphism on the incidence of T2DM in a sample of Iraqi patients. Iraqi Journal of Biotechnology 17(1): 1-5.
Potere, N.; Del Buono, M.G.; Mauro, A.G.; Abbate, A. & Toldo, S. 2019. Low density lipoprotein receptor-related protein-1 in cardiac inflammation and infarct healing. Frontiers in Cardiovascular Medicine 6, 51.
Qin, A.Y.; Zhang, X.W.; Liu, L.; Yu, J.P.; Li, H.; Wang, S.Z.E. & Cao, S. 2013. MiR-205 in cancer: an angel or a devil? European Journal of Cell Biology 92(2): 54-60.
Soro, A.; Jauhiainen, M.; Ehnholm, C. & Taskinen, M.R. 2003. Determinants of low HDL levels in familial combined hyperlipidemia. Journal of Lipid Research 44(8): 1536-1544.
Srivastava, R.A.K. 2018. Dysfunctional HDL in diabetes mellitus and its role in the pathogenesis of cardiovascular disease. Molecular and Cellular Biochemistry 440(1): 167-187.
Van De Sluis, B.; Wijers, M. & Herz, J.2017. News on the molecular regulation and function of hepatic LDLR and LRP1. Current Opinion in Lipidology 28(3): 241.
Wieczorek, E.; Ćwiklińska, A.; Kuchta, A.; Kortas-Stempak, B.; Gliwińska, A. & Jankowski, M. 2021. Decreased Efficiency of Very-Low-Density Lipoprotein Lipolysis Is Linked to Both Hypertriglyceridemia and Hypercholesterolemia, but It Can Be Counteracted by High-Density Lipoprotein. Nutrients 13(4): 1224.
Wong, B.; Kruse, G.; Kutikova, L.; Ray, K.K.; Mata, P. & Bruckert, E. 2016. Cardiovascular disease risk associated with familial hypercholesterolemia: a systematic review of the literature. Clinical Therapeutics 38(7): 1696-1709.
Xu, Y. & Fu, M. 2003. Alterations of HDL subclasses in hyperlipidemia. Clinica Chimica Acta 332(1-2): 95-102.
Xuan, Y.; Liu, S.; Li, Y.; Dong, J.; Luo, J.; Liu, T. & Sun, Z. 2017. Short term vagus nerve stimulation reduces myocardial apoptosis by downregulating microRNA 205 in rats with chronic heart failure. Molecular Medicine Reports 16(5): 5847-5854.