Chidzidzo Chitsva Chekuchengeta Mitsipa Yako Yakachena

Kumutsidzira nzira inodzikira patinenge takura kunogona kudzivirira kubva kune atherosclerosis, chikonzero chikuru chekurova kwemoyo uye sitiroko. Mune zvakaburitswa online nhasi mu Proceedings of the National Academy of Sciences (PNAS), masayendisiti kuAlbert Einstein College of Medicine inotungamirwa naAna Maria Cuervo, MD, Ph.D., vakabudirira kuderedza tsinga-inarrowing plaque mumakonzo dzingangogadzira izvo maronda. Vatsvakurudzi vakaita izvi nekusimudzira chaperone-mediated autophagy (CMA), nzira yekuchengetedza imba iyo Dr. Cuervo yakawana muna 1993 uye yakatumidzwa muna 2000. 

“Takaratidza mukutsvakurudza uku kuti tinoda CMA kuti idzivirire pachirwere che<em>atherosclerosis, icho chinova chakasimba uye chinofambira mberi apo CMA inoderera—chimwe chinhu chinoitikawo kana vanhu vakura,” akadaro Dr. Cuervo, purofesa we<em>development and molecular biology uye wemishonga. , Robert naRenée Belfer Sachigaro weChidzidzo cheNeurodegenerative Diseases, uye co-director weInstitute for Aging Research paEinstein. "Asi zvakakoshawo, takaratidza kuti kuwedzera kweCMA chiitiko kunogona kuve nzira inoshanda yekumisa atherosclerosis uye kumisa kufambira mberi kwayo."

Inonakidza CMA CV

CMA inoita kuti masero arambe achishanda zvakanaka nekusarudza kushatisa mapuroteni akawanda ane maseru. MuCMA, mapuroteni akasarudzika "chaperone" anosunga kumapuroteni mu cytoplasm uye anoatungamira kune enzyme-yakazadzwa masero maumbirwo anonzi lysosomes kuti achekwe uye ashandiswezve. Dr. Cuervo akatsanangura vazhinji vevatambi vemamolekoro vanobatanidzwa muCMA uye vakaratidza kuti CMA, kuburikidza nekuparara kwayo panguva yakakodzera yemapuroteni anokosha, inogadzirisa maitiro akawanda e intracellular kusanganisira glucose uye lipid metabolism, circadian rhythms uye DNA kugadzirisa. Akawanawo kuti yakakanganiswa CMA inobvumira mapuroteni akakuvadzwa kuti aungane kusvika kune chepfu, zvichikonzera kuchembera uye-kana muchetura buildup ukaitika mumasero etsinga-kuneurodegenerative zvirwere zvinosanganisira Parkinson's, Alzheimer's, uye Huntington's disease.

Zvakaitwa naDr. Cuervo zvakazivikanwa muna 2019 pavakasarudzwa kupinda muNational Academy of Sciences (NAS). Muna 1996, NAS yakatanga kukoka nhengo dzayo dzichangosarudzwa kuti dziendese Chinyorwa cheKutanga kuPNAS chaizosimbisa kubatsira kwenhengo yesainzi. Nekuda kwekunonoka kunoenderana neCCIDID-19, bepa ranhasi rekudzivirira kweCMA pakurwisa atherosclerosis ipepa raDr. Cuervo rekutanga PNAS uye rinowedzera kune rake basa rekukosha kweCMA.

Kurwisa Kudzokera Kurwisa Plaque

Chirwere chemwoyo (CVD) ndicho chiri kukonzera rufu pasi rose, uye vanopfuura 80% yeavo vanofa neCVD nekuda kwekurwadziwa kwemoyo uye sitiroko. CVD, zvakare, inowanzobatanidzwa neatherosclerosis: kuvakwa kweplaque (chinhu chinonamira chine mafuta, cholesterol, calcium, nezvimwe zvinhu) mukati memadziro etsinga. Kuunganidza plaque kunoomesa uye kutetepa tsinga, zvichidzitadzisa kuendesa ropa rine oxygen kumhasuru yemwoyo (zvinoita kuti mwoyo urwise), uropi (sitiroko), uye kumuviri wese.

Kuti vaongorore basa reCMA muatherosclerosis, Dr. Cuervo nevamwe vaaishanda navo vakakurudzira atherosclerosis mumakonzo nekuvadyisa kudya kweMadokero kwemafuta kwemavhiki e12 uye kutarisa basa reCMA muaorta yakakanganiswa neplaque yemhuka. Basa reCMA pakutanga rakawedzera mukupindura dambudziko rekudya; mushure memavhiki e12, zvisinei, kugadzirwa kweplaque kwakakosha, uye hapana basa reCMA raigona kuonekwa mumhando mbiri dzemasero-macrophages uye arterial smooth muscle masero-anozivikanwa kusashanda muatherosclerosis, zvichiita kuti pave nekuvakwa kweplaque mukati metsinga.

"CMA yakaita seyakakosha zvikuru mukudzivirira macrophages uye masero anotsvedzerera masero-achivabatsira kushanda zvakajairika pasinei nepro-atherosclerotic kudya-kamwe kwekanguva, kusvikira basa ravo reCMA rasvika pakumira," akadaro Dr. Cuervo. Akataura kuti kudyisa chikafu chine mafuta akawanda kune mbeva dzinoshaikwa zvachose muchiitiko cheCMA kwakaburitsa humbowo hwakasimba hwekukosha kweCMA: maplaque akakura kusvika makumi mana muzana pane ayo ari mukudzora mhuka dzaivewo pakudya kwemafuta akawanda.

Zvembeva uye Nezve Varume

Vatsvagiri vakawana humbowo hwekuti isina simba CMA chiitiko chinopindirana neatherosclerosis muvanhu zvakare. Vamwe varwere vakarohwa nesitiroko vanovhiyiwa, inozivikanwa secarotid endarterectomy, inobvisa zvikamu zvakakanganiswa neplaque yetsinga yavo yecarotid kuderedza njodzi yesitiroko kechipiri. Dr. Cuervo nevamwe vake vakaongorora basa reCMA muzvikamu zve carotid artery kubva kuvarwere vekutanga ve62 vakateverwa kwemakore matatu mushure mekuvhiyiwa kwavo.

"Vaya varwere vane mazinga akakwirira eCMA vachitevera kurohwa kwavo kwekutanga havana kumbowana yechipiri, asi kurohwa kwechipiri kwakaitika munenge varwere vose vane basa reCMA rakaderera," akadaro Dr. Cuervo. "Izvi zvinoratidza kuti chiitiko chako cheCMA post-endarterectomy chinogona kubatsira kufanotaura njodzi yako yekurohwa kechipiri uye mukutungamira kurapwa, kunyanya kune vanhu vane CMA yakaderera."

Kuvhura CMA, Kugadzirisa Atherosclerosis

Chidzidzo ichi ndicho chekutanga kuratidza kuti kuvhura CMA kunogona kuve nzira inoshanda yekudzivirira atherosclerosis kubva pakunyanya kana kufambira mberi. Vatsvakurudzi vane genetically "upregulated" CMA mumakonzo akadyiswa pro-atherosclerotic, mafuta akawanda ekuMadokero kudya uye gare gare akaaenzanisa nemakonzo ekudzora akadyiswa kudya kwakafanana kwemavhiki e12. Iwo CMA-akakwidziridzwa mbeva akange avandudza zvakanyanya eropa lipid profiles, aine zvakanyanya kuderedzwa mazinga echolesterol kana zvichienzaniswa nemakonzo ekudzora. Maronda eplaque akaumbwa mumakonzo akashandurwa ane genetic aive madiki uye akapfava mukuomarara kana achienzaniswa nemaplaque mukudzora mbeva. Sezvineiwo, vanhu havazodi genetic alteration kuti vabatsirwe nekutsvaga uku.

"Ini nevandinoshanda navo takagadzira mishonga yemishonga iyo yakaratidza kuvimbiswa kwekuchengeteka uye nekubudirira kuwedzera kweCMA basa mumasumbu akawanda emakonzo uye mumasero anotorwa nevanhu," akadaro Dr. Cuervo. Einstein akaisa pfuma yehungwaru pane iri pasi tekinoroji.

Pepa rePNAS rakanzi "Kudzivirira basa rechaperone-mediated autophagy kurwisa atherosclerosis." Vamwe vanyori veEinstein vaiva Julio Madrigal-Matute, Ph.D., Dario F. Riascos-Bernal, Antonio Diaz, MD, Ph.D., Inmaculada Tasset, Ph.D., Adrian Martin-Segura, Ph.D., Susmita Kaushik, Ph.D., Simoni Tiano, MD, Matthieu Bourdenx, Ph.D., Gregory J. Krause, MS, Nicholas Sibinga, MD, Fernando Macian, MD, Ph.D., naRajat Singh, MD Rimwe bepa anotsinhirana nemunyori ndiJudith C. Sluimer, Ph.D., weMaastricht University Medical Center muNetherlands uye University of Edinburgh muUnited Kingdom.