Iqembu le I-Sant Pau Research Institute (IR Sant Pau) yase-Barcelona ichaze indlela yebhayoloji esiza ukuqonda kangcono ukuthi injani i-cholesterol inqwabelana emithanjeni nokuthi kungani amanye ama-plaque egcina eyingozi kakhulu kunamanye. Lokhu okutholakele kuyingxenye yocwaningo lwe-atherosclerosis, isifo esingelapheki senhliziyo nemithambo yegazi esisengenye yezimbangela eziphambili zokufa eYurophu.
Imiphumela, eshicilelwe kujenali yesayensi AmaseliBakhomba ukugcwalisa i-C3, iphrotheni eyinhloko yamasosha omzimba, njengomdlali ophakathi nendawo ukuthuthukiswa kwezilonda ze-atheroscleroticNgaphandle komsebenzi wayo wakudala wokuzivikela ezifweni, le ngqamuzana ibamba iqhaza ngokuqondile ezinguqukweni zamangqamuzana ezenza ama-cholesterol plaque abe ntekenteke kakhudlwana futhi kube lula ukuqhekeka.
Indima engalindelekile yomphelelisi we-C3 ku-atherosclerosis
I-Atherosulinosis ibonakaliswa yizimpawu ukunqwabelana kwe-cholesterol nezinye izinto ezindongeni ze-arteryLokhu kubangela ukusabela kokuvuvukala okuqhubekayo. Ngokuhamba kwesikhathi, le nhlanganisela ye-lipids kanye nokuvuvukala kubangela ukuthi izicubu zemithambo yegazi zilungiswe futhi zilahlekelwe ukulinganisela kwazo namandla emishini.
Kulo mongo, iqembu le Ama-Biomarkers we-Cardiovascular Disease Evolution e-IR Sant Pau Ucwaningo lugxile ekugcwaliseni i-C3, iphrotheni emaphakathi yohlelo lokuhambisana. Ngokwesiko yaziwa ngendima yayo ekuvikelekeni kwemvelo, manje sekuboniswe ukuthi futhi inomthelela oqondile kumaseli akha udonga lwe-arterial.
Ngokusho komcwaningi ohamba phambili walolu cwaningo, Teresa PadróUcwaningo lukhomba indima entsha yomphelelisi we-C3 exhumanisa impendulo yokuzivikela komzimba ezindleleni zamaselula ezilungisa kabusha imithambo. Lokhu kunikeza umbono odidiyelwe kakhudlwana wokuthi i- Ukuvuvukala kanye ne-lipids "kuyahambisana" ukukhuthaza ukuqhubeka kwesifo.
Ucwaningo lubonisa ukuthi, uma lucushiwe, umphelelisi we-C3 unomthelela Izilonda ze-atherosclerotic ziba zingazinzile futhi zithambekele ekuqhekekeniLokhu kungazinzi kuyakhathaza ikakhulukazi ngoba ukuphuka kwe-plaque kungabangela ukwakheka kwe-thrombus futhi, ngenxa yalokho, kubangele i-myocardial infarction noma i-stroke.
Ababhali bagcizelela ukuthi ukuqonda le axis entsha yamangqamuzana kuvumela ukuqonda kangcono ukuthi kungani, kwabanye abantu, ama-plaque aqhubekela phambili ekuqondeni. amafomu ayingozi kakhulu yize lawula izici zakudala njenge-cholesterol yegazi noma umfutho wegazi, isici esithakasela kakhulu i-European cardiology.
Amaseli emisipha ebushelelezi, phakathi nendawo yoshintsho
Ngaphakathi kodonga lwe-arterial, i amangqamuzana emisipha ebushelelezi Badlala indima ebalulekile. Ngaphansi kwezimo ezijwayelekile, asebenza njengamaseli e-contractile, esiza ukugcina ukuqina kwemithambo yegazi nokulawula ithoni ye-vascular. Kodwa-ke, ekuphenduleni ukuvuvukala noma i-lipid stimuli, bangashintsha ukuziphatha kwabo.
Umsebenzi we-IR Sant Pau ubonisa ukuthi ukwenziwa kusebenze komphelelisi we-C3 kubangela a uchungechunge lwezinguquko kula maseli emisipha abusheleleziBayeka ukuziphatha njengamaseli enkontileka futhi bathole iphrofayela yeselula eyengeziwe, enamandla amakhulu okulungisa kabusha i-matrix ebazungezile nokubamba iqhaza ekwakhekeni kwe-atherosclerotic plaque.
Lolu shintsho kubunikazi beselula alukona, ngokwalo, olungalungile: luyingxenye ye izindlela zokulungisa zemvelo yomkhumbi lapho wonakele. Inkinga iphakama lapho le nqubo iqhubeka isikhathi eside endaweni egcwele i-cholesterol kanye nabalamuli abavuvukalayo, into evamile ekwelashweni okuthuthukisiwe kwe-atherosclerosis.
Kuleso simo, amangqamuzana emisipha abushelelezi angakwazi ukufaka isandla hhayi kuphela ekuqiniseni udonga lwe-arterial, kodwa Isakhiwo sepuleti sintekenteke kakhulungesembozo esincanyana futhi esisengozini enkulu ye-fibrous. Lezi zinhlobo zokulimala yizona ezivame ukuqhekeka noma ukuphuka.
Ngakho-ke ucwaningo lunikeza a incazelo enemininingwane ukuthi izindlela zokuzivikela zomzimba zisebenzisana kanjani nezinqubo zokuvuselela i-vascular, iphuzu kuze kube manje lingacaciswanga ngokugcwele ezincwadini zesayensi.
Ucezu lwe-iC3b nokuhlelwa kabusha kwangaphakathi kweseli
Enye yezinto ezibalulekile ezikhonjwe ithimba isiqeshana esicushiwe se-plugin eyaziwa ngokuthi iC3bLe molekyuli ikhiqizwa lapho i-C3 yenziwe yasebenza futhi isebenza njengesignali ehlela kabusha ingaphakathi lamaseli emisipha abushelelezi odonga lwe-arterial.
Abacwaningi babone ukuthi i-iC3b iyakwazi lungisa ukuhlelwa kwangaphakathi kwalawa maseliezithonya indlela ezinamathela ngayo endaweni yazo nokuthi zihamba kanjani ngaphakathi kodonga lomkhumbi. Lolu shintsho ekuziphatheni kwamaseli luxhumene ngqo nokuqhubekela phambili kwezilonda ze-atherosclerotic.
Ikakhulukazi, ucwaningo lugxile ku- i-paxillin (PXN)I-Paxillin iyiphrotheni eyinhloko ezindaweni zokunamathela kwamaseli ezilawula ukuxhumana kwamaseli ne-matrix ezungezile. Isebenza njengeplathifomu yokubonisa, eqondisayo ukuma kweseli, i-motility, nokuzinza.
Lisebenzisa amasu e-microscope athuthukisiwe, ithimba liqinisekise ukuthi lapho amangqamuzana emisipha abushelelezi echayeka kuwo i-aggregated low density lipoproteins (LDL-ag), uhlobo oluguquliwe lwe-cholesterol ebizwa ngokuthi "embi" evame ukunqwabelana emithanjeni, kukhona ukuncipha kwenani le-paxillin kanye noshintsho oluphawulekayo ekusabalaliseni kwayo ngaphakathi kweseli.
Le nhlanganisela ye-iC3b ne-agLDL iholela ku-a ukuhlelwa kabusha okujulile kwezakhiwo zamaselulaLokhu kusiza amaseli emisipha abushelelezi asebenzise i-phenotype efudukayo futhi elungiswa kabusha. Ngale ndlela, ama-plaque athambekele ekuguqukeni abe yizimo ezithuthuke kakhulu nezingazinzile, okwandisa ingozi yenhliziyo nemithambo yegazi.
Ukuvuvukala, i-lipids, nokuzinza kwe-arterial
Imiphumela yomsebenzi iqinisa umqondo wokuthi I-atherosulinosis ingaphezu nje kwediphozithi yamafutha emithanjeni. Kuyinqubo eguquguqukayo lapho ama-lipids, amangqamuzana amasosha omzimba, amangqamuzana odonga lwemithambo, nabalamuli abaningi abavuvukalayo bahlanganyela.
Uhlelo lwe-plugin, futhi ikakhulukazi i-C3 nocezu lwayo lwe-iC3b, manje seluvela njenge ukuxhumana phakathi kokuzivikela komzimba kanye nokuvuselelwa kwemithamboAyihlanganyeli kuphela ekuphenduleni kokuvuvukala kwakudala, kodwa futhi ibeka isimo, ukuziphatha nokuzinza kwamaseli asekela ukwakheka komthambo.
Esimweni saseYurophu, lapho i- Izifo zenhliziyo nemithambo yegazi zisaqhubeka ziyimbangela yokufa ehamba phambiliUkuqonda lezi zindlela ezicashile kuthola ukubaluleka komtholampilo. Amathuba okungenelela hhayi kuphela emazingeni e-cholesterol, kodwa futhi nasekuzinzeni kwe-plaque kanye nokusabela okuhlobene nokuvuvukala, kuvula izindlela ezintsha zokunciphisa izenzakalo ezifana nokuhlaselwa yinhliziyo nokushaywa unhlangothi.
Ababhali bocwaningo basikisela ukuthi le eksisi entsha yamangqamuzana ingasiza ekuchazeni ukuthi kungani, kwezinye iziguli, ama-plaque eba sengozini ikakhulukazi naphezu kokulawulwa okufanele kwezinto zakudala eziyingozi. Lolu hlobo lolwazi lungaba ukhiye kulo hlunga ukuhlukaniswa kwengozi futhi wenze ngendlela oyifisayo ukulandelela.
Ngaphezu kwalokho, umsebenzi ubeka umphelelisi we-C3 ngangokunokwenzeka umgomo wokwelapha wesikhathi esizayoUkushintsha ukusebenza kwayo noma ukuvimba imiphumela ethile ye-iC3b kumaseli emisipha abushelelezi, ngokombono, kungaba nomthelela ekuqiniseni ukuzinza kwemishini yemithambo ngaphandle kokuphazamisa ngokweqile ukuzivikela kukonke.
Imithelela yamasu amasha okwelapha
Ukuze uqonde kabanzi ukuthi ama-plugin e-C3 kanye ne-iC3b ayithonya kanjani i ukuzinza kwe-cholesterol plaque Lokhu kusivumela ukuthi sicabangele izindlela zokwelapha eziqondile. Ngaphandle kwezidakamizwa ezijwayelekile ezihloselwe ukwehlisa i-cholesterol noma ukuvuvukala kwesistimu, ukungenelela kungaklanywa okuqondise izinqubo zamaselula ezilungisa kabusha udonga lwe-arterial.
Abacwaningi kwa-IR Sant Pau baveza ukuthi, ngokusekelwe kulolu lwazi, kuzokwazi ukuhlola amasu lokho akugcini nje ukunciphisa umthwalo we-lipidkodwa futhi kuqinise ukumbozwa kwe-fibrous kwama-plaque futhi kuthuthukise ikhono lemithambo yegazi ukumelana nokucindezeleka kwansuku zonke kwemishini.
Izikhombisi-ndlela zesikhathi esizayo zihlanganisa izindlela zokwelapha ezingase zibe khona ezishintsha ngokukhetha ukusayina kwe-iC3b noma ezivikela amaprotheni esakhiwo abalulekile njenge-paxillin, ukuze kuvinjelwe amaseli emisipha ebushelelezi ukuthi angatholi i-phenotype efudukayo ngokweqile kanye nokuqeda uzinzo.
Lolu hlobo lwendlela luhambisana nokuthambekela kwamanje ku-cardiology yokuhlanganisa imithi enamandla yokwehlisa i-lipid (njengama-statins noma ama-PCSK9 inhibitors) anamasu anembe kakhudlwana okulwa nokuvuvukala. Ngaphezu kwalokho, ukuhlanganisa ukulawulwa kwezindlela zokulungisa kabusha i-arterial kunganikeza ukuvikeleka okwengeziwe ezigulini ezisengozini enkulu.
Ngamafuphi, ucwaningo olwenziwa e-Barcelona lwengeza esinye isiqeshana ku-puzzle eyinkimbinkimbi ye-atherosclerosis, ebonisa ukuthi kanjani a amaprotheni amasosha omzimba ajwayelekile Kungaba nomthelela omkhulu ekwakhiweni kwemithambo yegazi nasekuguqukeni komtholampilo kwalesi sifo.
Konke kusikisela ukuthi, njengoba sijula ​​kulezi zinhlobo zezindlela, kuzokwazi ukuklama izindlela zokwelapha ezihambisanayo ezingagcini nje ngokunciphisa i-cholesterol, kodwa futhi zigxile kuzo. ukwenza amapuleti azinze futhi angakwazi ukuphuka, ngomgomo oyinhloko wokunciphisa kakhulu izehlakalo zenhliziyo nemithambo yegazi kubantu.