{"id":3661,"date":"2020-09-24T17:15:15","date_gmt":"2020-09-24T15:15:15","guid":{"rendered":"https:\/\/www.mc-praha.cz\/mcp\/?p=3661"},"modified":"2020-10-02T16:09:38","modified_gmt":"2020-10-02T14:09:38","slug":"mitochondrie-jako-klic-k-zabraneni-srdecniho-selhani","status":"publish","type":"post","link":"https:\/\/www.mc-praha.cz\/mcp\/mitochondrie-jako-klic-k-zabraneni-srdecniho-selhani\/","title":{"rendered":"Mitochondrie jako kl\u00ed\u010d k zabr\u00e1n\u011bn\u00ed srde\u010dn\u00edho selh\u00e1n\u00ed"},"content":{"rendered":"

O mitochondri\u00edch, hlavn\u00edch dodavatel\u00edch energie pro t\u011blo, je v\u00edce sly\u0161et a\u017e v\u00a0posledn\u00edm desetilet\u00ed, kdy se objevuj\u00ed st\u00e1le nov\u00e9 a nov\u00e9 poznatky o t\u011bchto mal\u00fdch \u201eelektr\u00e1rn\u00e1ch\u201c. Zaj\u00edmav\u00e1 studie \u201eTargeting the Mitochondria in Heart Failure\u201c se zam\u011b\u0159uje na mitochondrie v\u00a0srde\u010dn\u00ed a kostern\u00ed svalovin\u011b a zkoum\u00e1, jak by se dalo zabr\u00e1nit mno\u017e\u00edc\u00edm se p\u0159\u00edpad\u016fm srde\u010dn\u00edho selh\u00e1n\u00ed, kter\u00e9 zvy\u0161uj\u00ed po\u010dty hospitalizac\u00ed, n\u00e1roky na zdravotn\u00ed p\u00e9\u010di a l\u00e9ky, a tak\u00e9 m\u00edru \u00famrtnosti. <\/strong><\/p>\n

K\u00a0srde\u010dn\u00edmu selh\u00e1n\u00ed doch\u00e1z\u00ed v\u00a0d\u016fsledku energetick\u00e9 deprivace. Na vin\u011b jsou mitochondrie \u2013 p\u0159edev\u0161\u00edm abnormality ve struktur\u00e1ch, dynamice a funkc\u00edch mitochondri\u00ed. Tyto p\u0159\u00edznaky maj\u00ed za n\u00e1sledek akumulaci \u0161kodliv\u00fdch reaktivn\u00edch forem kysl\u00edku (ROS, reactive oxygen species) a sn\u00ed\u017eenou produkci adenosin trifosf\u00e1tu (ATP). Oprava mitochondri\u00e1ln\u00edch dysfunkc\u00ed m\u016f\u017ee v\u00e9st k\u00a0nov\u00fdm terapeutick\u00fdm postup\u016fm, kter\u00e9 by mohly napomoci ke zv\u00fd\u0161en\u00ed srde\u010dn\u00ed funkce, m\u00edry p\u0159e\u017eit\u00ed pacient\u016f a kvality jejich \u017eivota.<\/p>\n

Ve zm\u00edn\u011bn\u00e9 studii je pops\u00e1na stavba mitochondri\u00ed a jejich funkce a tak\u00e9 procesy, ke kter\u00fdm v\u00a0mitochondri\u00edch v\u00a0r\u016fzn\u00fdch cyklech doch\u00e1z\u00ed p\u0159i transportu elektron\u016f. P\u0159i t\u011bchto transportech se tvo\u0159\u00ed ATP, jeho\u017e pr\u016fm\u011brn\u00fd \u010dlov\u011bk za jeden den vyprodukuje a spot\u0159ebuje asi 65 kg. Srde\u010dn\u00ed \u010dinnost spot\u0159ebuje denn\u011b 6 kg ATP a a\u017e 90 % bun\u011b\u010dn\u00e9ho ATP v\u00a0srdci je spot\u0159ebov\u00e1no na jeho chod.<\/p>\n

Jeliko\u017e ATP nelze uchov\u00e1vat, spr\u00e1vn\u00e1 tvorba t\u00e9to l\u00e1tky v\u00a0t\u011ble je velmi d\u016fle\u017eit\u00e1. V\u00a0pr\u016fb\u011bhu st\u00e1rnut\u00ed srdci doch\u00e1z\u00ed energie, jeliko\u017e mitochondrie u\u017e ji nedok\u00e1\u017eou produkovat v pot\u0159ebn\u00e9m mno\u017estv\u00ed. N\u00e1sledkem je\u00a0srde\u010dn\u00ed selh\u00e1n\u00ed.<\/p>\n

Uveden\u00e1 studie se d\u00e1le zab\u00fdv\u00e1 biogenez\u00ed mitochondri\u00ed, jejich f\u00faz\u00ed, procesem mitof\u00e1gie, jako\u017e i abnormalitami a rol\u00ed mitochondri\u00ed v\u00a0kostern\u00ed srde\u010dn\u00ed svalovin\u011b. D\u00e1le \u0159e\u0161\u00ed souvislosti mezi st\u00e1rnut\u00edm mitochondri\u00ed, mitochondri\u00e1ln\u00edmi abnormalitami a srde\u010dn\u00edm selh\u00e1n\u00edm. V\u011bt\u0161ina pacient\u016f, kter\u00e9 postihuje srde\u010dn\u00ed selh\u00e1n\u00ed, je star\u0161\u00ed 65 let. Mitochondrie je pova\u017eov\u00e1na za \u201einici\u00e1tora st\u00e1rnut\u00ed\u201c. M\u016f\u017ee tak\u00e9 doj\u00edt k\u00a0mutac\u00edm mitochondri\u00e1ln\u00ed DNA, co\u017e vede ke vzniku gen\u016f, kter\u00e9 st\u00e1rnut\u00ed urychluj\u00ed. Spolu s\u00a0mno\u017e\u00edc\u00edmi se mutacemi se sni\u017euje v\u00fdkon mitochondri\u00ed a doch\u00e1z\u00ed ke st\u00e1rnut\u00ed organismu. Mitochondrie v\u00a0kostern\u00ed svalovin\u011b jsou z\u00e1visl\u00e9 tak\u00e9 na produkci Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1\u03b1), kter\u00fd hraje hlavn\u00ed roli v\u00a0regulaci bun\u011b\u010dn\u00e9ho energetick\u00e9ho metabolismu. V\u011bt\u0161inou u d\u011bt\u00ed a star\u00fdch lid\u00ed m\u016f\u017eeme pozorovat slab\u0161\u00ed a ochablej\u0161\u00ed svaly.<\/p>\n

Zm\u00edn\u011bn\u00e1 studie pojedn\u00e1v\u00e1 tak\u00e9 o tom, jak lze mitochondrie opravovat, a o mo\u017en\u00e9m budouc\u00edm pou\u017eit\u00ed mitochondri\u00ed v terapii. Posledn\u00ed desetilet\u00ed p\u0159ineslo n\u011bkolik pr\u016flomov\u00fdch poznatk\u016f v\u00a0t\u00e9to oblasti. V\u00a0dne\u0161n\u00ed dob\u011b je srde\u010dn\u00ed selh\u00e1n\u00ed l\u00e9\u010deno pomoc\u00ed neurohormon\u00e1ln\u00ed medikace a operac\u00ed srdce (remodelingu). T\u00e9m\u011b\u0159 v\u0161echny tyto metody pracuj\u00ed se zv\u00fd\u0161en\u00edm a sn\u00ed\u017een\u00edm frekvence srde\u010dn\u00edho tepu (nap\u0159. bradykardie). Dosavadn\u00ed terapie se sna\u017e\u00ed ulevit od symptom\u016f, ale je t\u0159eba se specializovat p\u0159\u00edmo na \u0159e\u0161en\u00ed molekul\u00e1rn\u00edch abnormalit.<\/p>\n

Mezi metody zlep\u0161uj\u00edc\u00ed \u010dinnost mitochondri\u00ed pat\u0159\u00ed nap\u0159\u00edklad pou\u017eit\u00ed elamipretidu, kter\u00fd dok\u00e1\u017ee vyhledat mitochondrie, lokalizovat a penetrovat vnit\u0159n\u00ed membr\u00e1nu a spolupracovat s\u00a0kardiolipinem na obnov\u011b mitochondri\u00e1ln\u00edch bioenergetick\u00fdch proces\u016f. U ps\u016f bylo p\u0159i pou\u017eit\u00ed elamipretidu prok\u00e1z\u00e1no n\u011bkolik velice kladn\u00fdch v\u00fdsledk\u016f. Jeho dlouhodob\u00e9 pou\u017e\u00edv\u00e1n\u00ed dok\u00e1\u017ee tak\u00e9 zrenovovat tk\u00e1\u0148 kostern\u00ed svaloviny.<\/p>\n

Dal\u0161\u00ed metodou pro zlep\u0161en\u00ed \u010dinnosti mitochondri\u00ed je pou\u017eit\u00ed adenosinu, kter\u00fd dok\u00e1\u017ee v kardiomyocytech aktivovat mitochondri\u00e1ln\u00ed energetiku, v\u00e1pn\u00edkovou homeost\u00e1zu, a tak\u00e9 funkci a strukturu srde\u010dn\u00ed svaloviny. Vedlej\u0161\u00edmi \u00fa\u010dinky adenosinu jsou nap\u0159. vazokonstrikce, atrioventrikul\u00e1rn\u00ed blok nebo bradykardie. Jeho pozitivn\u00ed \u00fa\u010dinky v\u00a0boji proti srde\u010dn\u00edmu selh\u00e1n\u00ed v\u0161ak p\u0159eva\u017euj\u00ed.<\/p>\n

Z\u00e1v\u011brem lze konstatovat, \u017ee se \u00famrtnost i po\u010det hospitalizac\u00ed pacient\u016f se srde\u010dn\u00edm selh\u00e1n\u00edm nad\u00e1le zvy\u0161uj\u00ed. S\u00a0rostouc\u00edm st\u00e1rnut\u00edm populace se tato situace bude nejsp\u00ed\u0161e st\u00e1le zhor\u0161ovat. Nyn\u011bj\u0161\u00ed terapie vyu\u017e\u00edvan\u00e9 u srde\u010dn\u00edho selh\u00e1n\u00ed sni\u017euj\u00ed srde\u010dn\u00ed p\u0159et\u00ed\u017een\u00ed formou sn\u00ed\u017een\u00ed srde\u010dn\u00edho tepu, a t\u00edm energetick\u00e9 spot\u0159eby srdce. Oprava mitochondri\u00ed by umo\u017enila zlep\u0161it energetick\u00e9 z\u00e1sobov\u00e1n\u00ed srdce. Ve\u0161ker\u00e9 terapie slou\u017e\u00edc\u00ed k\u00a0oprav\u011b mitochondri\u00ed jsou v\u0161ak v\u00a0za\u010d\u00e1tc\u00edch. St\u00e1le nen\u00ed jasn\u00e9, zda je lep\u0161\u00ed opravovat mitochondrie po z\u00e1t\u011b\u017ei nebo v\u00a0klidov\u00e9m st\u00e1diu \u010di dle stupn\u011b pokro\u010dilosti nemoci.<\/p>\n

Ing. V\u00edt Smejkal<\/strong><\/p>\n

Odborn\u00fd asistent<\/p>\n

Zdroj:<\/p>\n

Sabbah HN (2020): Targeting the mitochondria in heart failure. JACC: Basic to Translational Science, 5, 88\u2013106.<\/p>\n","protected":false},"excerpt":{"rendered":"

O mitochondri\u00edch, hlavn\u00edch dodavatel\u00edch energie pro t\u011blo, je v\u00edce sly\u0161et a\u017e v\u00a0posledn\u00edm desetilet\u00ed, kdy se […]<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"image","meta":{"_uag_custom_page_level_css":""},"categories":[1],"tags":[],"uagb_featured_image_src":{"full":false,"thumbnail":false,"medium":false,"medium_large":false,"large":false,"1536x1536":false,"2048x2048":false,"boldthemes_grid":false,"boldthemes_grid_11":false,"boldthemes_grid_22":false,"boldthemes_grid_21":false,"boldthemes_grid_12":false,"boldthemes_latest_posts":false,"boldthemes_grid_gallery":false},"uagb_author_info":{"display_name":"Jbednar","author_link":"https:\/\/www.mc-praha.cz\/mcp\/author\/jbednar\/"},"uagb_comment_info":0,"uagb_excerpt":"O mitochondri\u00edch, hlavn\u00edch dodavatel\u00edch energie pro t\u011blo, je v\u00edce sly\u0161et a\u017e v\u00a0posledn\u00edm desetilet\u00ed, kdy se […]","post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/posts\/3661"}],"collection":[{"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/comments?post=3661"}],"version-history":[{"count":1,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/posts\/3661\/revisions"}],"predecessor-version":[{"id":3662,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/posts\/3661\/revisions\/3662"}],"wp:attachment":[{"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/media?parent=3661"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/categories?post=3661"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/tags?post=3661"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}