| Heart related complications in muscular | | | | Cardiac arrhythmias can be life threatening, and |
| dystrophies are serious concern. The | | | | muscular dystrophy patients should be monitored |
| cardiomyopathy and cardiac arrhythmias are | | | | closely for signs and symptoms of cardiac |
| caused by defects in cardiomyocyte and cardiac | | | | arrhythmia events. As with all cardiomyopathy |
| conduction system function. Unlike the skeletal | | | | patients, treatment aimed at arrhythmia |
| muscle degenerative process, for which | | | | prevention should be sought. And from this point |
| treatment options are currently limited, therapy is | | | | of view, ayurvedic therapies and remedies are |
| available for the cardiovascular complications. New | | | | good options. Mamsagmi Rasayana is a promising |
| therapies for muscle degeneration are moving into | | | | molecule being scientifically verified. Get more |
| clinical trials and are expected to also improve the | | | | assess at |
| cardiac function, longevity and wellbeing of | | | | References: |
| muscular dystrophy patients. | | | | 1. Laval SH and Bushby KM (2004) Limb-girdle |
| The muscular dystrophies are muscle destroying | | | | muscular dystrophies?from genetics to molecular |
| disorders. There are at least 21 different | | | | pathology. Neuropathol Appl Neurobiol 30: 91-105 |
| monogenic causes of muscular dystrophy, and | | | | 2. Lapidos KA et al. (2004) The dystrophin |
| cardiovascular complications are commonly | | | | glycoprotein complex: signaling strength and |
| associated with some subtypes.[1] Currently there | | | | integrity for the sarcolemma. Circ Res 94: |
| is no established cure but data available to support | | | | 1023-1031 |
| various anti-oxidants and ayurvedic herbs such as | | | | 3. Blake DJ and Martin-Rendon E (2002) |
| Curcuma longa and Terminalia arjuna, based | | | | Intermediate filaments and the function of the |
| approaches to management of cardio myopathy. | | | | dystrophin-protein complex. Trends Cardiovasc |
| Cardiomyopathy in the muscular dystrophies can | | | | Med 12: 224-228 |
| develop to heart failure. | | | | 4. Petrof BJ et al. (1993) Dystrophin protects the |
| There are several subtypes of muscular | | | | sarcolemma from stresses developed during |
| dystrophies, which are categorized based on | | | | muscle contraction. Proc Natl Acad Sci U S A 90: |
| genetics and molecular pathogenesis:- | | | | 3710-3714 |
| (1) The Dystrophin Glycoprotein Complex: Being | | | | 5. Danialou G et al. (2001) Dystrophin-deficient |
| important for membrane stability, it plays a | | | | cardiomyocytes are abnormally vulnerable to |
| particularly important part in the muscular | | | | mechanical stress-induced contractile failure and |
| dystrophies, because mutations in the genes that | | | | injury. Faseb J 15: 1655-1657 |
| encode its constituent proteins result in a distinct | | | | 6. Dellorusso C et al. (2001) Tibialis anterior |
| group of progressive degenerative muscle | | | | muscles in mdx mice are highly susceptible to |
| disorders. [2,3] Mutations in the genes encoding | | | | contraction-induced injury. J Muscle Res Cell Motil |
| dystrophin or the SARCOGLYCAN proteins cause | | | | 22: 467-475 |
| myofibers and cardio myocytes to be abnormally | | | | 7. Matsuda R et al. (1995) Visualization of |
| susceptible to contraction-induced | | | | dystrophic muscle fibers in mdx mouse by vital |
| damage.[4—6] The loss of the dystrophin | | | | staining with Evans blue: evidence of apoptosis in |
| protein, as occurs in most forms of Duchenne | | | | dystrophin-deficient muscle. J Biochem (Tokyo) |
| muscular dystrophy, is associated with | | | | 118: 959-964 |
| destabilization of all the dystrophin-associated | | | | 8. McLaurin MD et al. (1997) Cardiac troponin I, |
| proteins, including the sarcoglycans. [7] Membrane | | | | cardiac troponin T, and creatine kinase MB in |
| instability in cardiomyocyte and skeletal myofibers | | | | dialysis patients without ischemic heart disease: |
| is associated with leakage of muscle-specific | | | | evidence of cardiac troponin T expression in |
| enzymes into the serum. Creatine kinase levels | | | | skeletal muscle. Clin Chem 43: 976-982 |
| are substantially raised in these patients, and both | | | | 9. Moreira ES et al. (2000) Limb-girdle muscular |
| the MM and MB isoforms are detected. Elevation | | | | dystrophy type 2G is caused by mutations in the |
| of the MB isoform often indicates cardiomyocyte | | | | gene encoding the sarcomeric protein telethonin. |
| degeneration. | | | | Nat Genet 24: 163-166 |
| (2) Telethonin, Titin and Myotilin: Mutations in these | | | | 10. Hauser MA et al. (2000) Myotilin is mutated in |
| genes lead to rare forms of muscular | | | | limb girdle muscular dystrophy 1A. |
| dystrophy.[9—13] Telethonin is thought to be | | | | Hum Mol Genet 9: 2141-2147 |
| important for passive stretch in cardiomyocytes. | | | | 11. Hackman P et al. (2002) Tibial muscular |
| (3) Nuclear Membrane Proteins: The LMNA gene | | | | dystrophy is a titinopathy caused by mutations in |
| encodes the inner nuclear membrane proteins | | | | TTN,the gene encoding the giant skeletal-muscle |
| lamin A & C. They regulate a number of | | | | protein titin. Am J Hum Genet 71: 492-500 |
| nuclear processes, including DNA replication, | | | | 12. Knoll R et al. (2002) The cardiac mechanical |
| transcription, chromatin attachments and nuclear | | | | stretch sensor machinery involves a Z disc |
| transport.[14] | | | | complex that is defective in a subset of human |
| (4) Additional Membrane-Associated Proteins: | | | | dilated cardiomyopathy. Cell 111: 943-955 |
| Dysferlin is a transmembrane protein that binds | | | | 13. Omens JH et al. (2002) Muscle LIM protein |
| phospholipids in a calcium dependent manner and is | | | | deficiency leads to alterations in passive ventricular |
| highly expressed in skeletal and cardiac | | | | mechanics. Am J Physiol Heart Circ Physiol 282: |
| muscle.[15—18] Mutations in DYSF result in | | | | H680-H687 |
| abnormal muscle membrane repair. | | | | 14. Ostlund C and Worman HJ (2003) Nuclear |
| New experimental therapies for muscular | | | | envelope proteins and neuromuscular diseases. |
| dystrophies are now emerging. Gene replacement | | | | Muscle Nerve 27: 393-406 |
| therapy, Ayurvedic Rasayana based therapies are | | | | 15. Bashir R et al. (1998) A gene related to |
| also being explored for the regeneration of | | | | Caenorhabditis elegans spermatogenesis factor |
| muscles. The cardiac problems associated with | | | | fer-1 is mutated in limb-girdle muscular dystrophy |
| some forms of muscular dystrophy sometimes | | | | type 2B. Nat Genet 20: 37-42 |
| need treatment. Terminalia Arjuna has remarkable | | | | 16. Anderson LV et al. (1999) Dysferlin is a plasma |
| cardio protective, heart muscle strengthening | | | | membrane protein and is expressed early in |
| properties. Current scientific research has proved | | | | human development. Hum Mol Genet 8: 855-861 |
| that plant contains specific medically active | | | | 17. Davis DB et al. (2002) Calcium-sensitive |
| constituents namely triterpine glycosides like | | | | phospholipid binding properties of normal and |
| arjunetosides I, II, III, IV, arjunine and arjunetein, | | | | mutant ferlin C2 domains. J Biol Chem 277: |
| phytosterols, rich in minerals like calcium, | | | | 22883-22888 |
| magnesium, zinc and copper. Regular use of | | | | 18. Liu J et al. (1998) Dysferlin, a novel skeletal |
| Arjuna improves pumping activity of heart, | | | | muscle gene, is mutated in Miyoshi myopathy and |
| improves cardiac muscle strength, decrease in | | | | limb girdle muscular dystrophy. Nat Genet 20: |
| LDL cholesterol levels. It has been reported to | | | | 31-36 |
| possess protective cardiovascular and | | | | 19. Alpana Rama, P. Lauria, R Gupta, et al (1997): |
| hypolipidemic properties.[19-20] Finally, | | | | Hypocholesterolaemic effects of Terminalia |
| growth-factor-based gene therapy is emerging as | | | | Arjuna, Journal of Ethno pharmacology, Vol 55:3, |
| a successful approach for stimulating muscle | | | | 1997, Pages 165-169 |
| growth. | | | | 20. |