性别与增龄所致心肌纤维化
Gender and Aging Lead to Myocardial Fibrosis
DOI: 10.12677/ACM.2022.12111446, PDF,   
作者: 王云会：重庆医科大学附属第二医院老年病科，重庆 ；邓 玮：重庆医科大学附属第二医院全科医学，重庆
关键词: 心肌纤维化；增龄；性别；雌激素；雄激素；Myocardical Fibrosis； Aging； Gender； Estrogen； Androgen
摘要: 心肌纤维化是老化心脏的重要特征，其严重程度随着年龄增长逐渐加重，可损害心脏结构。在增龄过程中，不同性别的心肌纤维化严重程度及纤维化类型不同。老年男性总心肌纤维化程度(替代性纤维化 + 反应性纤维化)更高，但以哪一类型为主尚不清楚，而老年女性以反应性纤维化为主，这可能与雌激素、雄激素对心肌纤维化发生发展的影响有关。因此，探索性别影响增龄所致心肌纤维化的因素，为将来针对老年人提供更多的抗纤维化治疗靶点，进而改善老年人生活质量。
Abstract: Myocardial fibrosis is an important feature of the aging heart, and its increasing severity with age can damage the heart structure. During aging, the severity of myocardial fibrosis and the type of fi-brosis are different. The degree of total myocardial fibrosis (alternative fibrosis + reactive fibrosis) is higher in older men, but it is unclear which type is predominant, while older women are mainly reactive fibrosis, which may be related to the influence of estrogen and androgen on the occurrence and development of myocardial fibrosis. Therefore, the factors affecting myocardial fibrosis caused by gender should be explored to provide more antifibrotic therapeutic targets for the elderly, and then improve the quality of life in the elderly.
文章引用：王云会, 邓玮. 性别与增龄所致心肌纤维化[J]. 临床医学进展, 2022, 12(11): 10026-10033. https://doi.org/10.12677/ACM.2022.12111446

参考文献

[1] Dai, D.F., Chen, T., Johnson, S.C., Szeto, H. and Rabinovitch, P.S. (2012) Cardiac Aging: From Molecular Mechanisms to Significance in Human Health and Disease. Antioxidants & Redox Signaling, 16, 1492-1526. [Google Scholar] [CrossRef] [PubMed]
[2] Sangaralingham, S.J., Wang, B.H., Huang, L., et al. (2016) Cardiorenal Fibrosis and Dysfunction in Aging: Imbalance in Mediators and Regulators of Collagen. Peptides, 76, 108-114. [Google Scholar] [CrossRef] [PubMed]
[3] Frangogiannis, N.G. (2019) The Extracellular Matrix in Is-chemic and Nonischemic Heart Failure. Circulation Research, 125, 117-146. [Google Scholar] [CrossRef] 
[4] Maruyama, K. and Imanaka-Yoshida, K. (2022) The Pathogenesis of Cardiac Fibrosis: A Review of Recent Progress. International Journal of Molecular Sciences, 23, Article No. 2617. [Google Scholar] [CrossRef] [PubMed]
[5] de Boer, R.A., De Keulenaer, G., Bauersachs, J., et al. (2019) Towards Better Definition, Quantification and Treatment of Fibrosis in Heart Failure. A Scientific Roadmap by the Committee of Translational Research of the Heart Failure Association (HFA) of the European Society of Cardiology. European Journal of Heart Failure, 21, 272-285. [Google Scholar] [CrossRef] [PubMed]
[6] 高小燕, 邓春玉, 饶芳, 等. 衰老与心肌纤维化[J]. 医学综述, 2018, 24(24): 4785-4789.
[7] Tang, X., Li, P.H. and Chen, H.Z. (2020) Cardiomyocyte Senescence and Cellular Communi-cations within Myocardial Microenvironments. Frontiers in Endocrinology, 11, Article 280. [Google Scholar] [CrossRef] [PubMed]
[8] Achkar, A., Saliba, Y. and Fares, N. (2020) Differential Gen-der-Dependent Patterns of Cardiac Fibrosis and Fibroblast Phenotypes in Aging Mice. Oxidative Medicine and Cellular Longevity, 2020, Article ID: 8282157. [Google Scholar] [CrossRef] [PubMed]
[9] Liu, C.Y., Liu, Y.C., Wu, C., et al. (2013) Evaluation of Age-Related Interstitial Myocardial Fibrosis with Cardiac Magnetic Resonance Contrast-Enhanced T1 Mapping: MESA (Multi-Ethnic Study of Atherosclerosis). Journal of the American College of Cardiology, 62, 1280-1287. [Google Scholar] [CrossRef] [PubMed]
[10] Miyamoto, S. (2019) Autophagy and Cardiac Aging. Cell Death & Differentiation, 26, 653-664. [Google Scholar] [CrossRef] [PubMed]
[11] Shirakabe, A., Ikeda, Y., Sciarretta, S., Zablocki, D.K. and Sadoshima, J. (2016) Aging and Autophagy in the Heart. Circulation Research, 118, 1563-1576. [Google Scholar] [CrossRef] 
[12] Tastet, L., Kwiecinski, J., Pibarot, P., et al. (2020) Sex-Related Differences in the Extent of Myocardial Fibrosis in Patients with Aortic Valve Stenosis. Cardiovascular Imaging, 13, 699-711. [Google Scholar] [CrossRef] [PubMed]
[13] Kararigas, G., Dworatzek, E., Petrov, G., et al. (2012) Sex-Dependent Regulation of Fibrosis and Inflammation in Human Left Ventricular Remodelling under Pres-sure Overload. European Journal of Heart Failure, 16, 1160-1167. [Google Scholar] [CrossRef] [PubMed]
[14] Yusifov, A., Woulfe, K.C. and Bruns, D.R. (2022) Mechanisms and Implica-tions of Sex Differences in Cardiac Aging. The Journal of Cardiovascular Aging, 2, Article No. 20. [Google Scholar] [CrossRef] [PubMed]
[15] Hung, C.L., Gonçalves, A., Shah, A.M., et al. (2017) Age- and Sex-Related Influences on Left Ventricular Mechanics in Elderly Individuals Free of Prevalent Heart Failure: The ARIC Study (Atherosclerosis Risk in Communities). Circulation: Cardiovascular Imaging, 10, e004510. [Google Scholar] [CrossRef] 
[16] Olivetti, G., Giordano, G., Corradi, D., et al. (1995) Gender Differences and Aging: Effects on the Human Heart. Journal of the American College of Cardiology, 26, 1068-1079. [Google Scholar] [CrossRef] [PubMed]
[17] Leri, A., Kajstura, J., Li, B., et al. (2000) Cardio-myocyte Aging Is Gender-Dependent: The Local IGF-1-IGF-1R System. Heart Disease (Hagerstown, Md.), 2,108-115.
[18] Ivey, M.J., Kuwabara, J.T., Riggsbee, K.L. and Tallquist, M.D. (2019) Platelet-Derived Growth Factor Receptor-α Is Essential for Cardiac Fibroblast Survival. American Journal of Physiology-Heart and Circulatory Physi-ology, 317, H330-H344. [Google Scholar] [CrossRef] [PubMed]
[19] Petrov, G., Regitz-Zagrosek, V., Lehmkuhl, E., et al. (2010) Regression of Myocardial Hypertrophy after Aortic Valve Replacement: Faster in Women? Circulation, 122, S23-S28. [Google Scholar] [CrossRef] 
[20] Kane, A.E., Bisset, E.S., Heinze-Milne, S., et al. (2021) Maladaptive Changes Associated with Cardiac Aging Are Sex-Specific and Graded by Frailty and Inflammation in C57BL/6 Mice. The Journals of Gerontology: Series A, 76, 233-243. [Google Scholar] [CrossRef] [PubMed]
[21] Dworatzek, E., Mahmoodzadeh, S., Schriever, C., et al. (2019) Sex-Specific Regulation of Collagen I and III Expression by 17β-Estradiol in Cardiac Fibroblasts: Role of Estrogen Re-ceptors. Cardiovascular Research, 115, 315-327. [Google Scholar] [CrossRef] [PubMed]
[22] Iorga, A., Cunningham, C.M., Moazeni, S., et al. (2017) The Protective Role of Estrogen and Estrogen Receptors in Cardiovascular Disease and the Controversial Use of Estrogen Therapy. Bi-ology of Sex Differences, 8, Article No. 33. [Google Scholar] [CrossRef] [PubMed]
[23] Arcones, A.C., Martínez-Cignoni, M.R., Vila-Bedmar, R., et al. (2021) Cardiac GRK2 Protein Levels Show Sexual Dimorphism during Aging and Are Regulated by ovarian Hormones. Cells, 10, Article No. 673. [Google Scholar] [CrossRef] [PubMed]
[24] Lieu, M., Traynham, C.J., de Lucia, C., et al. (2020) Loss of Dynamic Regulation of G Protein-Coupled Receptor Kinase 2 by Nitric Oxide Leads to Cardiovascular Dysfunction with Aging. American Journal of Physiology-Heart and Circulatory Physiology, 318, H1162-H1175. [Google Scholar] [CrossRef] [PubMed]
[25] Arcones, A.C., Murga, C., Penela, P., Inserte, J. and Mayor Jr., F. (2021) G protein-Coupled Receptor Kinase 2 at Crossroads of Metabolic and Cardiovascular Diseases. Current Opinion in Endocrine and Metabolic Research, 16, 75-85. [Google Scholar] [CrossRef] 
[26] Woodall, M.C., Woodall, B.P., Gao, E., Yuan, A. and Koch, W.J. (2016) Cardiac Fibroblast GRK2 Deletion Enhances Contractility and Remodeling Following Ischemia/Reperfusion In-jury. Circulation Research, 119, 1116-1127. [Google Scholar] [CrossRef] 
[27] Lenhart, P.M., Broselid, S., Barrick, C.J., Leeb-Lundberg, L.M.F. and Caron, K.M. (2013) G-Protein Coupled Receptor 30 Interacts with Receptor Activity Modifying Protein 3 and Confers Sex-Dependent Cardioprotection. Journal of Molecular Endocrinology, 51, 191-202. [Google Scholar] [CrossRef] 
[28] Wang, X., Ma, J., Zhang, S., et al. (2021) G Protein-Coupled Estrogen Receptor 30 Reduces Transverse Aortic Constriction-Induced Myocardial Fibrosis in Aged Female Mice by Inhibiting the ERK1/2 -MMP-9 Signaling Pathway. Frontiers in Pharmacology, 12, Article 731609. [Google Scholar] [CrossRef] [PubMed]
[29] Liu, D., Zhan, Y., Ono, K., et al. (2022) Pharmacological Activa-tion of Estrogenic Receptor G Protein-Coupled Receptor 30 Attenuates Angiotensin II-Induced Atrial Fibrosis in Ovari-ectomized Mice by Modulating TGF-β1/Smad Pathway. Molecular Biology Reports, 49, 6341-6355. [Google Scholar] [CrossRef] [PubMed]
[30] Sickinghe, A.A., Korporaal, S.J.A., Den Ruijter, H.M. and Kessler, E.L. (2019) Estrogen Contributions to Microvascular Dysfunction Evolving to Heart Failure with Preserved Ejection Fraction. Frontiers in Endocrinology, 10, Article 442. [Google Scholar] [CrossRef] [PubMed]
[31] Montalvo, C., Villar, A.V., Merino, D., et al. (2012) Androgens Contribute to Sex Differences in Myocardial Remodeling under Pressure Overload by a Mechanism Involving TGF-β. PLOS ONE, 7, e35635. [Google Scholar] [CrossRef] [PubMed]
[32] Froese, N., Wang, H., Zwadlo, C., et al. (2018) An-ti-Androgenic Therapy with Finasteride Improves Cardiac Function, Attenuates Remodeling and Reverts Pathologic Gene-Expression after Myocardial Infarction in Mice. Journal of Molecular and Cellular Cardiology, 122, 114-124. [Google Scholar] [CrossRef] [PubMed]
[33] Papamitsou, T., Barlagiannis, D., Papaliagkas, V., Kotanidou, E. and Dermentzopoulou-Theodoridou, M. (2011) Testosterone-Induced Hypertrophy, Fibrosis and Apoptosis of Cardiac Cells—An Ultrastructural and Immunohistochemical Study. Medical Science Monitor, 17, BR266-BR273. [Google Scholar] [CrossRef] 
[34] Wadthaisong, M., Witayavanitkul, N., Bupha-Intr, T., Wattanaperm-pool, J. and de Tombe, P.P. (2019) Chronic High- Dose Testosterone Treatment: Impact on Rat Cardiac Contractile Bi-ology. Physiological Reports, 7, e14192. [Google Scholar] [CrossRef] [PubMed]
[35] Chung, C.C., Hsu, R.C., Kao, Y.H., et al. (2014) Androgen Attenuates Cardiac Fibroblasts Activations through Modulations of Transforming Growth Factor-β and Angiotensin II Signaling. International Journal of Cardiology, 176, 386-393. [Google Scholar] [CrossRef] [PubMed]
[36] Chung, C.C., Lin, Y.K., Kao, Y.H., Lin, S.H. and Chen, Y.J. (2021) Physiological Testosterone Attenuates Profibrotic Activities of Rat Cardiac Fibroblasts through Modulation of Nitric Oxide and Calcium Homeostasis. Endocrine Journal, 68, 307-315. [Google Scholar] [CrossRef] 
[37] Chung, C.C., Kao, Y.H., Chen, Y.J. and Chen, Y-.J. (2013) An-drogen Modulates Cardiac Fibrosis Contributing to Gender Differences on Heart Failure. The Aging Male, 16, 22-27. [Google Scholar] [CrossRef] [PubMed]
[38] Ikeda, Y., Aihara, K., Sato, T., et al. (2005) Androgen Re-ceptor Gene Knockout Male Mice Exhibit Impaired Cardiac Growth and Exacerbation of Angiotensin II-Induced Cardiac Fibrosis. Journal of Biological Chemistry, 280, 29661- 29666. [Google Scholar] [CrossRef] 
[39] Chen, F., Song, F., Chen, Y., et al. (2019) Exogenous Testosterone Alleviates Cardiac Fibrosis and Apoptosis via Gas6/Axl Pathway in the Senescent Mice. Experimental Gerontology, 119,128-137. [Google Scholar] [CrossRef] [PubMed]
[40] DuPont, J.J., Kim, S.K., Kenney, R.M. and Jaffe, I.Z. (2021) Sex Differences in the Time Course and Mechanisms of Vascular and Cardiac Aging in Mice: Role of the Smooth Muscle Cell Mineralocorticoid Receptor. American Journal of Physiology-Heart and Circulatory Physiology, 320, H169-H180. [Google Scholar] [CrossRef] [PubMed]
[41] Kim, S.K., McCurley, A.T., DuPont, J.J., et al. (2018) Smooth Muscle Cell—Mineralocorticoid Receptor as a Mediator of Cardiovascular Stiffness with Aging. Hypertension, 71, 609-621. [Google Scholar] [CrossRef] 
[42] Gordon, E.H., Peel, N.M., Samanta, M., et al. (2018) Sex Differences in Frailty: A Systematic Review and Meta- Analysis. Experimental Gerontology, 89, 30-40. [Google Scholar] [CrossRef] [PubMed]
[43] Kane, A.E., Keller, K.M., Heinze-Milne, S., et al. (2019) A Mu-rine Frailty Index Based on Clinical and Laboratory Measurements: Links between Frailty and Pro-Inflammatory Cyto-kines Differ in a Sex-Specific Manner. The Journals of Gerontology: Series A, 74, 275-282. [Google Scholar] [CrossRef] [PubMed]

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