Skip to main content

Advertisement

SpringerLink
Log in

Compensation: A Contemporary Regulatory Machinery in Cardiovascular Diseases?

  • Published:
Cardiovascular Toxicology Aims and scope Submit manuscript

Abstract

Both clinical and experimental findings at the molecular, cellular, tissue, organ and systematic levels have depicted the presence of a contemporary regulatory machinery namely compensation in various forms of cardiovascular diseases. Compensation is believed to be present and regulated within the scope of a biological entity and represents the initiation of dyshomeostasis. Compensation can be identified in multiple categories and organs in cardiovascular diseases at multiple levels. The capacity to reduce the unfavorable pathological compensation may be a criterion to evaluate the therapeutic effectiveness for cardiovascular diseases. This mini-review tries to take compensation into consideration in the understanding of onset and progression of cardiovascular diseases in particular, and thus, better or optimal therapeutic approaches may be achieved for the prevention and management of cardiovascular diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Gustafson-Wagner, E. A., Sinn, H. W., Chen, Y. L., Wang, D. Z., Reiter, R. S., Lin, J. L., et al. (2007). Loss of mXinalpha, an intercalated disk protein, results in cardiac hypertrophy and cardiomyopathy with conduction defects. American Journal of Physiology. Heart and Circulatory Physiology, 293, H2680–H2692.

    Article  PubMed  CAS  Google Scholar 

  2. Izumo, S., Lompre, A. M., Matsuoka, R., Koren, G., Schwartz, K., Nadal-Ginard, B., et al. (1987). Myosin heavy chain messenger RNA and protein isoform transitions during cardiac hypertrophy. Interaction between hemodynamic and thyroid hormone-induced signals. Journal of Clinical Investigation, 79, 970–977.

    Article  PubMed  CAS  Google Scholar 

  3. Anilkumar, N., Sirker, A., & Shah, A. M. (2009). Redox sensitive signaling pathways in cardiac remodeling, hypertrophy and failure. Frontiers in Bioscience, 14, 3168–3187.

    Article  PubMed  CAS  Google Scholar 

  4. Li, H. H., Willis, M. S., Lockyer, P., Miller, N., McDonough, H., Glass, D. J., et al. (2007). Atrogin-1 inhibits Akt-dependent cardiac hypertrophy in mice via ubiquitin-dependent coactivation of Forkhead proteins. Journal of Clinical Investigation, 117, 3211–3223.

    Article  PubMed  CAS  Google Scholar 

  5. Schwartz, K., de la Bastie, D., Bouveret, P., Oliviero, P., Alonso, S., & Buckingham, M. (1986). Alpha-skeletal muscle actin mRNA’s accumulate in hypertrophied adult rat hearts. Circulation Research, 59, 551–555.

    Article  PubMed  CAS  Google Scholar 

  6. Xia, Y., Wen, H. Y., Young, M. E., Guthrie, P. H., Taegtmeyer, H., & Kellems, R. E. (2003). Mammalian target of rapamycin and protein kinase a signaling mediate the cardiac transcriptional response to glutamine. Journal of Biological Chemistry, 278, 13143–13150.

    Article  PubMed  CAS  Google Scholar 

  7. Bourajjaj, M., Armand, A. S., da Costa Martins, P. A., Weijts, B., van der Nagel, R., Heeneman, S., et al. (2008). NFATc2 is a necessary mediator of calcineurin-dependent cardiac hypertrophy and heart failure. Journal of Biological Chemistry, 283, 22295–22303.

    Article  PubMed  CAS  Google Scholar 

  8. Skurk, C., Izumiya, Y., Maatz, H., Razeghi, P., Shiojima, I., Sandri, M., et al. (2005). The FOXO3a transcription factor regulates cardiac myocyte size downstream of AKT signaling. Journal of Biological Chemistry, 280, 20814–20823.

    Google Scholar 

  9. Bush, E. W., Hood, D. B., Papst, P. J., Chapo, J. A., Minobe, W., Bristow, M. R., et al. (2006). Canonical transient receptor potential channels promote cardiomyocyte hypertrophy through activation of calcineurin signaling. Journal of Biological Chemistry, 281, 33487–33496.

    Article  PubMed  CAS  Google Scholar 

  10. Seth, M., Sumbilla, C., Mullen, S. P., Lewis, D., Klein, M. G., Hussain, A., et al. (2004). Sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) gene silencing and remodeling of the Ca2+ signaling mechanism in cardiac myocytes. Proceedings of the National academy of Sciences of the United States of America, 101, 16683–16688.

    Article  PubMed  CAS  Google Scholar 

  11. Abe, Y., Ono, K., Kawamura, T., Wada, H., Kita, T., Shimatsu, A., et al. (2007). Leptin induces elongation of cardiac myocytes and causes eccentric left ventricular dilatation with compensation. American Journal of Physiology. Heart and Circulatory Physiology, 292, H2387–H2396.

    Article  PubMed  CAS  Google Scholar 

  12. Karmazyn, M., Purdham, D. M., Rajapurohitam, V., & Zeidan, A. (2007). Leptin as a cardiac hypertrophic factor: a potential target for therapeutics. Trends in Cardiovascular Medicine, 17, 206–211.

    Article  PubMed  CAS  Google Scholar 

  13. Ren, J. (2004). Leptin and hyperleptinemia—from friend to foe for cardiovascular function. Journal of Endocrinology, 181, 1–10.

    Article  PubMed  CAS  Google Scholar 

  14. Muraski, J. A., Fischer, K. M., Wu, W., Cottage, C. T., Quijada, P., Mason, M., et al. (2008). Pim-1 kinase antagonizes aspects of myocardial hypertrophy and compensation to pathological pressure overload. Proceedings of the National academy of Sciences of the United States of America, 105, 13889–13894.

    Article  PubMed  CAS  Google Scholar 

  15. Honsho, S., Nishikawa, S., Amano, K., Zen, K., Adachi, Y., Kishita, E., et al. (2009). Pressure-mediated hypertrophy and mechanical stretch induces IL-1 release and subsequent IGF-1 generation to maintain compensative hypertrophy by affecting Akt and JNK pathways. Circulation Research, 105, 1149–1158.

    Article  PubMed  CAS  Google Scholar 

  16. Kolwicz, S. C., Jr, & Tian, R. (2011). Glucose metabolism and cardiac hypertrophy. Cardiovascular Research, 90, 194–201.

    Article  PubMed  CAS  Google Scholar 

  17. Yamashita, H., Bharadwaj, K. G., Ikeda, S., Park, T. S., & Goldberg, I. J. (2008). Cardiac metabolic compensation to hypertension requires lipoprotein lipase. American Journal of Physiology-Endocrinology and Metabolism, 295, E705–E713.

    Article  PubMed  CAS  Google Scholar 

  18. Lebrin, F. & Mummery, C. L. (2008). Endoglin-mediated vascular remodeling: mechanisms underlying hereditary hemorrhagic telangiectasia. Trends in Cardiovascular Medicine, 18, 25–32.

    Article  PubMed  CAS  Google Scholar 

  19. Sanchez-Elsner, T., Botella, L. M., Velasco, B., Langa, C., & Bernabeu, C. (2002). Endoglin expression is regulated by transcriptional cooperation between the hypoxia and transforming growth factor-beta pathways. Journal of Biological Chemistry, 277, 43799–43808.

    Article  PubMed  CAS  Google Scholar 

  20. ten Dijke, P., Goumans, M. J., & Pardali, E. (2008). Endoglin in angiogenesis and vascular diseases. Angiogenesis, 11, 79–89.

    Article  PubMed  Google Scholar 

  21. Young, L. H., Renfu, Y., Russell, R., Hu, X., Caplan, M., Ren, J., et al. (1997). Low-flow ischemia leads to translocation of canine heart GLUT-4 and GLUT-1 glucose transporters to the sarcolemma in vivo. Circulation, 95, 415–422.

    Article  PubMed  CAS  Google Scholar 

  22. Young, L. H., Russell, R. R., I. I. I., Yin, R., Caplan, M. J., Ren, J., Bergeron, R., et al. (1999). Regulation of myocardial glucose uptake and transport during ischemia and energetic stress. American Journal of Cardiology, 83, 25H–30H.

    Article  PubMed  CAS  Google Scholar 

  23. Yang, J., & Holman, G. D. (2005). Insulin and contraction stimulate exocytosis, but increased AMP-activated protein kinase activity resulting from oxidative metabolism stress slows endocytosis of GLUT4 in cardiomyocytes. Journal of Biological Chemistry, 280, 4070–4078.

    Article  PubMed  CAS  Google Scholar 

  24. Severino, A., Campioni, M., Straino, S., Salloum, F. N., Schmidt, N., Herbrand, U., et al. (2007). Identification of protein disulfide isomerase as a cardiomyocyte survival factor in ischemic cardiomyopathy. Journal of the American College of Cardiology, 50, 1029–1037.

    Article  PubMed  CAS  Google Scholar 

  25. Feng, H. Z., Chen, M., Weinstein, L. S., & Jin, J. P. (2008). Removal of the N-terminal extension of cardiac troponin I as a functional compensation for impaired myocardial beta-adrenergic signaling. Journal of Biological Chemistry, 283, 33384–33393.

    Article  PubMed  CAS  Google Scholar 

  26. Atluri, P., Morine, K. J., Liao, G. P., Panlilio, C. M., Berry, M. F., Hsu, V. M., et al. (2007). Ischemic heart failure enhances endogenous myocardial apelin and APJ receptor expression. Cellular & Molecular Biology Letters, 12, 127–138.

    Article  CAS  Google Scholar 

  27. Chong, A. Y., Caine, G. J., Freestone, B., Blann, A. D., & Lip, G. Y. (2004). Plasma angiopoietin-1, angiopoietin-2, and angiopoietin receptor tie-2 levels in congestive heart failure. Journal of the American College of Cardiology, 43, 423–428.

    Article  PubMed  CAS  Google Scholar 

  28. Peng, W., Zhang, Y., Zhu, W., Cao, C. M., & Xiao, R. P. (2009). AMPK and TNF-alpha at the crossroad of cell survival and death in ischaemic heart. Cardiovascular Research, 84, 1–3.

    Article  PubMed  CAS  Google Scholar 

  29. Seta, Y., Shan, K., Bozkurt, B., Oral, H., & Mann, D. L. (1996). Basic mechanisms in heart failure: the cytokine hypothesis. Journal of Cardiac Failure, 2, 243–249.

    Article  PubMed  CAS  Google Scholar 

  30. Mann, D. L. (2002). Inflammatory mediators and the failing heart: past, present, and the foreseeable future. Circulation Research, 91, 988–998.

    Article  PubMed  CAS  Google Scholar 

  31. Valgimigli, M., Rigolin, G. M., Fucili, A., Porta, M. D., Soukhomovskaia, O., Malagutti, P., et al. (2004). CD34+ and endothelial progenitor cells in patients with various degrees of congestive heart failure. Circulation, 110, 1209–1212.

    Article  PubMed  CAS  Google Scholar 

  32. Nonaka-Sarukawa, M., Yamamoto, K., Aoki, H., Nishimura, Y., Tomizawa, H., Ichida, M., et al. (2007). Circulating endothelial progenitor cells in congestive heart failure. International Journal of Cardiology, 119, 344–348.

    Article  PubMed  Google Scholar 

  33. Bupha-Intr, T., Wattanapermpool, J., Pena, J. R., Wolska, B. M., & Solaro, R. J. (2007). Myofilament response to Ca2+ and Na+/H+ exchanger activity in sex hormone-related protection of cardiac myocytes from deactivation in hypercapnic acidosis. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 292, R837–R843.

    Article  PubMed  CAS  Google Scholar 

  34. Son, S. M. (2007). Role of vascular reactive oxygen species in development of vascular abnormalities in diabetes. Diabetes Research and Clinical Practice, 77(Suppl 1), S65–S70.

    Article  PubMed  CAS  Google Scholar 

  35. Brownlee, M. (2001). Biochemistry and molecular cell biology of diabetic complications. Nature, 414, 813–820.

    Article  PubMed  CAS  Google Scholar 

  36. Cheng, Z., Tseng, Y., & White, M. F. (2010). Insulin signaling meets mitochondria in metabolism. Trends in Endocrinology and Metabolism, 21, 589–598.

    Article  PubMed  CAS  Google Scholar 

  37. Sutak, R., Xu, X., Whitnall, M., Kashem, M. A., Vyoral, D., & Richardson, D. R. (2008). Proteomic analysis of hearts from frataxin knockout mice: marked rearrangement of energy metabolism, a response to cellular stress and altered expression of proteins involved in cell structure, motility and metabolism. Proteomics, 8, 1731–1741.

    Article  PubMed  CAS  Google Scholar 

  38. Duan, D. (2009). Phenomics of cardiac chloride channels: the systematic study of chloride channel function in the heart. Journal of Physiology, 587, 2163–2177.

    Article  PubMed  CAS  Google Scholar 

  39. Yamamoto-Mizuma, S., Wang, G. X., Liu, L. L., Schegg, K., Hatton, W. J., Duan, D., et al. (2004). Altered properties of volume-sensitive osmolyte and anion channels (VSOACs) and membrane protein expression in cardiac and smooth muscle myocytes from Clcn3-/- mice. Journal of Physiology, 557, 439–456.

    Article  PubMed  Google Scholar 

  40. Riordan, M. M., & Kovacs, S. J. (2008). Elucidation of spatially distinct compensatory mechanisms in diastole: radial compensation for impaired longitudinal filling in left ventricular hypertrophy. Journal of Applied Physiology, 104, 513–520.

    Article  PubMed  Google Scholar 

  41. AlDabal, L., & BaHammam, A. S. (2010). Cheyne-stokes respiration in patients with heart failure. Lung, 188, 5–14.

    Article  PubMed  CAS  Google Scholar 

  42. Fueger, P. T., Li, C. Y., Ayala, J. E., Shearer, J., Bracy, D. P., Charron, M. J., et al. (2007). Glucose kinetics and exercise tolerance in mice lacking the GLUT4 glucose transporter. Journal of Physiology, 582, 801–812.

    Article  PubMed  CAS  Google Scholar 

  43. Ziegler, M. A., Distasi, M. R., Bills, R. G., Miller, S. J., Alloosh, M., Murphy, M. P., et al. (2010). Marvels, mysteries, and misconceptions of vascular compensation to peripheral artery occlusion. Microcirculation, 17, 3–20.

    Article  PubMed  Google Scholar 

  44. Bacci, D., Valecchi, D., Sgambati, E., Gulisano, M., Conti, A. A., Molino-Lova, R., et al. (2008). Compensatory collateral circles in vertebral and carotid artery occlusion. Italian Journal of Anatomy and Embryology, 113, 265–271.

    PubMed  Google Scholar 

  45. Gross, C. G. (2009). Three before their time: Neuroscientists whose ideas were ignored by their contemporaries. Experimental Brain Research, 192, 321–334.

    Article  Google Scholar 

  46. Amit, I., Citri, A., Shay, T., Lu, Y., Katz, M., Zhang, F., et al. (2007). A module of negative feedback regulators defines growth factor signaling. Nature Genetics, 39, 503–512.

    Article  PubMed  CAS  Google Scholar 

  47. Harbuz, M. (2002). Neuroendocrine function and chronic inflammatory stress. Experimental Physiology, 87, 519–525.

    Article  PubMed  CAS  Google Scholar 

  48. Kikkawa, Y., Kameda, K., Hirano, M., Sasaki, T., & Hirano, K. (2010). Impaired feedback regulation of the receptor activity and the myofilament Ca2+ sensitivity contributes to increased vascular reactiveness after subarachnoid hemorrhage. Journal of Cerebral Blood Flow and Metabolism, 30, 1637–1650.

    Article  PubMed  CAS  Google Scholar 

  49. Mancia, G., Seravalle, G., Giannattasio, C., Bossi, M., Preti, L., Cattaneo, B. M., et al. (1992). Reflex cardiovascular control in congestive heart failure. American Journal of Cardiology, 69, 17G–22G.

    Article  PubMed  CAS  Google Scholar 

  50. Nollo, G., Faes, L., Porta, A., Pellegrini, B., Ravelli, F., Del, G. M., et al. (2002). Evidence of unbalanced regulatory mechanism of heart rate and systolic pressure after acute myocardial infarction. American Journal of Physiology. Heart and Circulatory Physiology, 283, H1200–H1207.

    PubMed  CAS  Google Scholar 

  51. Brandman, O., & Meyer, T. (2008). Feedback loops shape cellular signals in space and time. Science, 322, 390–395.

    Article  PubMed  CAS  Google Scholar 

  52. Besedovsky, H., & Sorkin, E. (1977). Network of immune-neuroendocrine interactions. Clinical and Experimental Immunology, 27, 1–12.

    PubMed  CAS  Google Scholar 

  53. Nabel, E. G. (2003). Cardiovascular disease. New England Journal of Medicine, 349, 60–72.

    Article  PubMed  CAS  Google Scholar 

  54. Jackson, J. G., & Pereira-Smith, O. M. (2006). Primary and compensatory roles for RB family members at cell cycle gene promoters that are deacetylated and downregulated in doxorubicin-induced senescence of breast cancer cells. Molecular and Cellular Biology, 26, 2501–2510.

    Article  PubMed  CAS  Google Scholar 

  55. Goldstein, J. L., & Brown, M. S. (1977). The low-density lipoprotein pathway and its relation to atherosclerosis. Annual Review of Biochemistry, 46, 897–930.

    Article  PubMed  CAS  Google Scholar 

  56. Fan, X. J., Yu, H., & Ren, J. (2011). Homeostasis and compensatory homeostasis: bridging Western medicine and traditional chinese medicine. Current Cardiology Reviews, 7, 43–46.

    Article  PubMed  Google Scholar 

  57. Aviram, M. (1999). Macrophage foam cell formation during early atherogenesis is determined by the balance between pro-oxidants and anti-oxidants in arterial cells and blood lipoproteins. Antioxidants & Redox Signaling, 1, 585–594.

    Article  CAS  Google Scholar 

  58. Lecour, S., Smith, R. M., Woodward, B., Opie, L. H., Rochette, L., & Sack, M. N. (2002). Identification of a novel role for sphingolipid signaling in TNF alpha and ischemic preconditioning mediated cardioprotection. Journal of Molecular and Cellular Cardiology, 34, 509–518.

    Article  PubMed  CAS  Google Scholar 

  59. Nakano, M., Knowlton, A. A., Dibbs, Z., & Mann, D. L. (1998). Tumor necrosis factor-alpha confers resistance to hypoxic injury in the adult mammalian cardiac myocyte. Circulation, 97, 1392–1400.

    Article  PubMed  CAS  Google Scholar 

  60. Siragy, H. (1999). Angiotensin II receptor blockers: review of the binding characteristics. American Journal of Cardiology, 84, 3S–8S.

    Article  PubMed  CAS  Google Scholar 

  61. Calhoun, D. A., Jones, D., Textor, S., Goff, D. C., Murphy, T. P., Toto, R. D., et al. (2008). Resistant hypertension: Diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation, 117, e510–e526.

    Article  PubMed  Google Scholar 

  62. Smiley, D., & Umpierrez, G. (2007). Metformin/rosiglitazone combination pill (Avandamet) for the treatment of patients with Type 2 diabetes. Expert Opinion on Pharmacotherapy, 8, 1353–1364.

    Article  PubMed  CAS  Google Scholar 

  63. Blansfield, J. A., Caragacianu, D., Alexander, H. R., I. I. I., Tangrea, M. A., Morita, S. Y., Lorang, D., et al. (2008). Combining agents that target the tumor microenvironment improves the efficacy of anticancer therapy. Clinical Cancer Research, 14, 270–280.

    Article  PubMed  CAS  Google Scholar 

  64. Dorrell, M. I., Aguilar, E., Scheppke, L., Barnett, F. H., & Friedlander, M. (2007). Combination angiostatic therapy completely inhibits ocular and tumor angiogenesis. Proceedings of the National academy of Sciences of the United States of America, 104, 967–972.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Kehong Zhang from the Ivy Editing for insightful comments and suggestions.

Author information

Authors and Affiliations

  1. China Nepstar Chain Drugstore Ltd., Hangzhou, 310003, Zhejiang, China

    Xiu-Juan Fan

  2. Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY, 82071, USA

    Jun Ren

Authors
  1. Xiu-Juan Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jun Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xiu-Juan Fan or Jun Ren.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fan, XJ., Ren, J. Compensation: A Contemporary Regulatory Machinery in Cardiovascular Diseases?. Cardiovasc Toxicol 12, 275–284 (2012). https://doi.org/10.1007/s12012-012-9167-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12012-012-9167-x

Keywords

Search

Navigation