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Percutaneous transluminal raum angioplasty attenuates post-stenotic raum mitochondrial puas

Mar 18, 2022

Hu rau: Audrey Huaudrey.hu@wecistanche.com

Percutaneous transluminal raum angioplasty attenuates post-stenotic raum mitochondrial puas nyob rau hauv npua nrog raum hlab ntsha stenosis thiab metabolic syndrome.

Rahele A.Farahani, Mohsen Afarideh & et al.

Abstract

Lub Hom Phiaj:Percutaneous transluminal raum angioplasty(PTRA) tau siv los kho tus kab mob renovascular (RVD), ib qho mob ntev uas tshwm sim los ntawm lub raum ischemia thiab metabolic abnormalities. Kev raug mob Mitochondrial tau cuam tshuam raws li lub hauv paus pathogenic mechanism hauv RVD (Renovascular disease), tab sis seb nws puas tuaj yeem thim rov qab los ntawm PTRA (Percutaneous transluminal raum angioplasty) tseem tsis paub meej. Peb xav tias PTRA(Percutaneous transluminal raum angioplasty)attenuates mitochondrial kev puas tsuaj, lub raum raug mob, thiab ua tsis taus pa nyob rau hauv npua nrog coexisting lub raum hlab ntsha stenosis (RAS) thiab metabolic syndrome (MetS).

Txoj kev: Plaub pawg npua (n{0}} txhua) tau kawm tom qab 16 lub lis piam ntawm kev noj zaub mov vim MetS thiab RAS (lub raum hlab ntsha stenosis) (MetS ntxiv rau RAS), MetS ntxiv rau RAS kho 4 lub lis piam ua ntej nrog PTRA(Percutaneous transluminal raum angioplasty), thiab Lean thiab MetS Sham tswj. Ib lub raum raum cov ntshav khiav (RBF) thiab glomerular filtration rate (GFR) tau soj ntsuam hauv-vivo nrog ntau tus ntes-CT, thiab lub raum tubular mitochondrial qauv thiab kev ua haujlwm thiab lub raum raug mob ex-vivo.

Cov txiaj ntsig: PTRA(Percutaneous transluminal raum angioplasty)ua tiav rov qab rau lub raum hlab ntsha patency, tab sis txhais tau tias cov hlab ntsha siab tseem tsis hloov pauv. Stenotic raum RBF thiab GFR, uas poob hauv MetS ntxiv rau RAS (lub raum hlab ntsha stenosis) piv rau MetS, sawv tom qab PTRA(Percutaneous transluminal raum angioplasty). PTRA attenuated MetS plus RAS (lub raum hlab ntsha stenosis)-vim mitochondrial structural abnormalities nyob rau hauv tubular hlwb thiab peritubular capillary endothelial hlwb txo mitochondrial H202 ntau lawm thiab nce raum cytochrome-c oxidase-TV kev ua si thiab ATP ntau lawm. PTRA(Percutaneous transluminal raum angioplasty)kuj txhim kho cortical microvascular thiab peritubular capillary ntom thiab ameliorated tubular raug mob thiab tubulointerstitial fibrosis hauv cov hlab ntsha.post-stenotic raum. Qhov tseem ceeb, lub raum mitochondrial puas cuam tshuam nrog kev raug mob tom qab stenotic thiab tsis ua haujlwm.

Xaus: Lub raum revascularization attenuated mitochondrial raug mob thiab txhim kho lub raum hemodynamics thiab ua haujlwm hauv swinepost-stenotic raum. Txoj kev tshawb no qhia txog kev hloov kho tshiab uas PTRA(Percutaneous transluminal raum angioplasty)Tej zaum yuav muaj txiaj ntsig zoo hauv kev ua kom muaj kev puas tsuaj mitochondrial thiab txhim kho lub raum ua haujlwm hauv kev sib koom ua ke MetS thiab RAS (lub raum hlab ntsha stenosis).

Ntsiab lus: Kab mob Renovascular; Lub raum hlab ntsha stenosis; Metabolic syndrome; Mitochondria; Ntshav siab; Revascularization

restore kidney function

Taw qhia

Tus kab mob Renovascular (RVD) vim yog atherosclerotic lub raum hlab ntsha stenosis (RAS) yog ib qho ua rau mob ntshav siab thib ob uas tshwm sim ntau zaus hauv cov neeg laus thiab tuaj yeem cuam tshuam txog 6.8 feem pua ​​​​ntawm cov neeg laus dua 65 xyoo (Hansen li al.. 2002).RVD (Renovascular disease) suav txog ntau tus neeg mob tshiab uas nkag mus rau hauv cov kev pab cuam lim ntshav hauv Asmeskas thiab cuam tshuam nrog ntau yam teeb meem hauv plawv plawv (Textor & Lerman, 2015)

Ntau qhov kev sim tshuaj suav nrog Cov Kab Mob Ntshav Qab Zib rau Lub Raum Artery Lesions (CORAL) kev sim (Cooper li al.2014) pom tias rov kho lub raum ntshav ntws (RBF) los ntawmpercutaneous transluminal raum angioplasty(PTRA) hauv RVD (Cov kab mob Renovascular) tsis muab cov txiaj ntsig ntxiv dua li kev kho mob raws li kev tiv thaiv kev kho mob plawv. Txawm li cas los xij, cov kev tshawb fawb yav tom ntej tau pom tias PTRA(Percutaneous transluminal raum angioplasty)tej zaum yuav muaj cov txiaj ntsig tseem ceeb hauv kev kho mob thiab cov txiaj ntsig kev tuag hauv cov neeg mob uas muaj kev pheej hmoo siab (Ritchie li al., 2014), tseem muaj kev xaiv kho mob rau cov neeg mob uas muaj RVD (Renovascular disease).

Metabolic Syndrome (MetS) yog ib pawg ntawm cov kab mob plawv ntsig txog kab mob uas feem ntau nrog RAS (lub raum hlab ntsha stenosis) thiab cuam tshuam nrog rau lub raum tsis zoo tom qab lub raum.

revascularization (Davies et al, 2010). Mets tuaj yeem suav txog ntau dua 50 feem pua ​​​​ntawm cov neeg mob uas qhia txog kev cuam tshuam rau lub raum thiab cuam tshuam nrog cov txiaj ntsig ntawm lub raum txo qis thiab nce kev nce mus rau hemodialysis tom qab PTRA.(Percutaneous transluminal raum angioplasty)(Davies et al., 2010). Txawm li cas los xij, qhov cuam tshuam ntawm PT(Percutaneous transluminal raum angioplasty)) ntawm lub hauv paus tseem ceeb ntawm cov txheej txheem lom neeg lub luag haujlwm rau kev kis kab mob hauv MetS ntxiv rau RAS (lub raum hlab ntsha stenosis) tseem yuav tau piav qhia.

Lub raum yog lub cev xav tau lub zog siab uas yuav tsum muaj ntau ntawm mitochondria, ob chav-membrane organelles uas tsim cov adenosine triphosphate (ATP) thiab tswj lwm yam tseem ceeb ntawm tes xws li kev ciaj sia, kev loj hlob, apoptosis, thiab tsim cov pa oxygen hom (ROS) (McFarland). , Taylor, & Turnbull, 2007). Nyob rau xyoo kaum xyoo dhau los, cov ntaub ntawv pov thawj kev sim ua rau muaj kev raug mob mitochondrial nyob rau hauv pathogenesis ntawm MetS thiab RAS (lub raum hlab ntsha stenosis). Peb tau pom yav dhau los tias npua nrog RAS (lub raum hlab ntsha stenosis) thiab MetS nthuav tawm lub raum mitochondrial structural abnormalities thiab dysfunction (Eirin li al., 2014; Eirin et al 2017). Peb kuj tseem tsis ntev los no tau pom tias kev sib koom ua ke RAS (lub raum hlab ntsha stenosis) thiab MetS synergistically aggravate mitochondrial structural kev puas tsuaj thiab ua haujlwm tsis zoo, thiab ua rau muaj kev raug mob thiab ua haujlwm tsis zoo hauv lub cev.post-stenotic raum(Nargesi, Zhang, thiab al, 2019). Txawm li cas los xij, seb MetS ntxiv rau RAS (lub raum hlab ntsha stenosis)-vim lub raum mitochondrial puas tuaj yeem thim rov qab los ntawm PTRA.(Percutaneous transluminal raum angioplasty)tseem tsis paub meej. Yog li, txoj kev tshawb fawb tam sim no tau sim qhov kev xav tias PTRA(Percutaneous transluminal raum angioplasty)attenuatespost-stenotic raummitochondrial puas nyob rau hauv npua nrog coexisting MetS thiab RAS (lub raum hlab ntsha stenosis).


treatment of kidney disease

Cov txiaj ntsig

Rau lub lis piam tom qab induction ntawm RAS (lub raum hlab ntsha stenosis) thiab tam sim ntawd ua ntej PTRA(Percutaneous transluminal raum angioplasty), tsis kho MetS ntxiv rau RAS npua thiab MetS ntxiv rau RAS npua muab rau PTRA ua tiav hemodynamically tseem ceeb stenosis (79.2 feem pua ​​​​4.7 feem pua ​​vs,73.3 feem pua ​​​​5.6 feem pua, p=0.44 ANOVA), thiab lawv cov ntshav siab tau nce siab piv rau Lean pigs (p<0.05 in="" all).="" table="" i="" summarizes="" the="" baseline="" characteristics="" and="" renal="" function="" in="" lean,="" mets,="" mets+ras="" (renal="" artery="" stenosis),="" and="" mets+ras+ptra="" groups="" 4="" weeks="" later.="" bodyweight="" was="" elevated="" in="" all="" mets="" groups="" compared="" to="" lean,="" as="" were="" systolic,="" diastolic,="" and="" mean="" arterial="" pressure.="" circulating="" isoprostane="" levels="" were="" higher="" in="" mets="" compared="" to="" lean,="" and="" further="" and="" similarly="" increased="" in="" mets+ras="" (renal="" artery="" stenosis)="" and="" mets+ras+ptra="" groups.="" contrarily,="" serum="" creatinine="" levels="" that="" were="" higher="" in="" mets+ras="" (renal="" artery="" stenosis)="" compared="" to="" lean="" and="" mets,="" decreased="" in="">(Percutaneous transluminal raum angioplasty). Ib lub raum ntim, RBF, thiab GFR tau siab dua hauv MetS piv rau Lean npua, txo qis hauv MetS ntxiv rau RAS (lub raum hlab ntsha stenosis), tab sis nce hauv PTRA-kho npua.

PTRA(Percutaneous transluminal raum angioplasty) txhim kho lub raum mitochondrial ntom thiab qauv

Immunoreactivity ntawm mitochondrial marker TOM-20 tshwm sim raws li cov pob txha ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntom ntu TOM , qhia txog kev txhim kho lub raum mitochondrial ntom. Lub raum tubular cell mitochondrial cheeb tsam thiab ib puag ncig tau siab dua hauv MetS ntxiv rau RAS (lub raum hlab ntsha stenosis) piv rau Lean thiab MetS, tab sis txo qis hauv MetS ntxiv RAS ntxiv rau PTRA(Percutaneous transluminal raum angioplasty), whereas lub raum tubular cell mitochondrial matrix ntom uas txo qis hauv MetS ntxiv rau RAS (lub raum hlab ntsha stenosis) piv rau Lean thiab MetS, nce hauv PTRA-kho npua. Podocyte mitochondrial cheeb tsam thiab ib puag ncig tau qis dua hauv MetS thiab MetS ntxiv rau RAS pawg piv rau Lean thiab tseem tsis hloov pauv tom qab PTRA(Percutaneous transluminal raum angioplasty). Contrarily, podocyte mitochondrial matrix ntom me ntsis hauv MetS piv rau Lean, ntxiv thiab zoo sib xws hauv MetS ntxiv rau RAS (lub raum hlab ntsha stenosis) thiab MetS ntxiv RAS ntxiv rau PTRA.(Percutaneous transluminal raum angioplasty)npua. PTCEC mitochondrial cheeb tsam thiab ib puag ncig tau siab dua MetS ntxiv rau RAS (lub raum hlab ntsha stenosis) piv rau Lean thiab MetS, tab sis txo qis hauv MetS ntxiv RAS ntxiv rau PTRA, qhov PTCEC mitochondrial matrix ntom tau txo qis hauv MetS ntxiv rau RAS (lub raum hlab ntsha stenosis) piv rau Lean thiab MetS. , nce hauv PTRA-kho npua.

PTRA (Percutaneous transluminal raum angioplasty) txhim kho lub raum mitochondrial muaj nuj nqi

Kev tsim tawm ntawm H202 hauv kev sib cais mitochondria tau nce siab hauv MetS thiab nce ntxiv hauv MetS ntxiv rau RAS (lub raum hlab ntsha stenosis), tab sis txo qis hauv MetS ntxiv rau RAS ntxiv rau PTRA-kho npua. Mitochondrial COX-IV kev ua haujlwm thiab ATP tiam tau txo qis hauv MetS piv rau Lean thiab qis dua hauv MetS ntxiv rau RAS (lub raum hlab ntsha stenosis), txhim kho hauv PTRA(Percutaneous transluminal raum angioplasty)- kho npua.

PTRA (Percutaneous transluminal raum angioplasty) txhim kho lub raum microvasculature

Qhov ntom ntom ntawm cortical microvessels poob qis hauv MetS thiab txo qis hauv MetS ntxiv rau RAS (lub raum hlab ntsha stenosis), tab sis txhim kho hauv MetS ntxiv rau RAS ntxiv rau PTRA. Microvascular tortuosity (qhia tias immaturity) tau siab dua hauv MetS piv rau Lean thiab nce ntxiv hauv MetS ntxiv rau RAS (lub raum hlab ntsha stenosis), tab sis normalized hauv PTRA.(Percutaneous transluminal raum angioplasty)-kho npua, whereas peritubular capillary ntom txo nyob rau hauv MetS thiab ntxiv txo nyob rau hauv MetS ntxiv RAS txhim kho nyob rau hauv PTRA-kho npua.

PTRA (Percutaneous transluminal raum angioplasty) ameliorated tubular raug mob thiab fibrosis

Lub raum superoxide ntau lawm hauv MetScompared rau Lean, thiab ntxiv thiab zoo sib xws hauv MetS ntxiv rau RAS (lub raum hlab ntsha stenosis) thiab MetS ntxiv rau RAS (lub raum hlab ntsha stenosis) ntxiv rau PTRA pawg. Txawm li cas los xij, kev raug mob ntawm tubular tau siab dua hauv MetS piv rau Lean, ntxiv rau MetS ntxiv rau RAS (lub raum hlab ntsha stenosis), tab sis txo qis hauv PTRA.(Percutaneous transluminal raum angioplasty)- kho npua, zoo li tubulointerstitial fibrosis. Piv txwv li, glomerular qhab nia zoo sib xws hauv MetS ntxiv rau RAS thiab MetS ntxiv RAS ntxiv rau PTRA piv rau Lean thiab MetS.

Lub raum mitochondrial puas correlated nrog post-stenotic raug mob

Zuag qhia tag nrho lub raum mitochondrial ntom correlated ncaj qha nrog stenotic-mob raum GFR, whereas lub raum tubular cell-matrix ceev correlated inversely nrog post-stenotic tubular raug mob. Ib qho kev sib cuam tshuam rov qab kuj tau pom ntawm PTCEC mitochondrial cheeb tsam thiab cov naj npawb ntawm peritubular capillaries hauv lub raum ischemic. Ntxiv mus, mitochondrial ATP tiam correlated inversely nrog tubulointerstitial fibrosis.


treatment of post-stenotic kidney

Kev sib tham

Txoj kev tshawb fawb tam sim no qhia tau hais tias lub raum revascularization muaj peev xwm txo qis kev raug mob mitochondrial hauv lub raum.post-stenotic raumntawm npua nrog kev sib koom ua ke MetS thiab RAS (lub raum hlab ntsha stenosis). Peb pom tias PTRA (Percutaneous transluminal raum angioplasty) uas tau ua tiav rov qab rau lub raum cov hlab ntsha patency thiab txhim kho RBF thiab GFR 4 lub lis piam tom qab ntawd kuj tau txo qis MetS ntxiv rau RAS (lub raum hlab ntsha stenosis)-vim mitochondrial structural abnormalities thiab ROS ntau lawm, thiab txhim kho bioenergetics. Lub raum revascularization kuj txhim kho cortical microvascular thiab peritubular capillary ntom thiab ameliorated tubular raug mob thiab tubulointerstitial fibrosis hauv cov hlab ntsha.post-stenotic raum. Qhov tseem ceeb, kev puas tsuaj rau lub raum mitochondrial cuam tshuam nrog kev raug mob tom qab stenotic thiab kev ua haujlwm tsis zoo, qhia txog lub luag haujlwm ntawm kev raug mob mitochondrial hauv lub hauv paus ntawm lub raum puas hauv MetS ntxiv rau RAS. Yog li, cov kev soj ntsuam no qhia txog kev kho mob tseem ceeb rau PTRA (Percutaneous transluminal raum angioplasty) hauv ameliorating mitochondrial kev puas tsuaj thiab txhim kho lub raum ua haujlwm hauv kev sim mob ntev MetS ntxiv rau RAS (lub raum hlab ntsha stenosis).

RAS (lub raum hlab ntsha stenosis) tseem yog ib qho tseem ceeb rau cov kab mob hauv lub raum kawg, cuam tshuam nrog rau lub raum raug mob, mob ntshav siab, plawv tsis ua hauj lwm, thiab kev mob plawv ntau ntxiv (Conlon, Little, Pieper, & Mark, 2001). Ob peb qhov kev sim tshuaj ntsuam xyuas yav tom ntej, suav nrog kev sim CORAL (Cooper et al.2014), Angioplasty thiab Stenting for Renal Artery Lesions (ASTRAL) trial (Investigators et al., 2009), thiab Stent Placement and Blood Pressure and Lipid- Kev txo qis rau kev tiv thaiv kev loj hlob ntawm lub raum tsis ua haujlwm tshwm sim los ntawm Atherosclerotic Ostial Stenosis ntawm Lub Raum Artery (STAR) sim (Bax li al, 2009) tau qhia tias lub raum hlab ntsha stenting nrog PTRA (Percutaneous transluminal raum angioplasty) ua rau muaj kev txwv tsis pub rov qab los ntawm lub raum ua haujlwm thiab tsis muab cov txiaj ntsig ntxiv dua li cov kev kho mob ib txwm muaj (Herrmann, Saad, & Textor, 2015). Txawm li cas los xij, kev tshawb fawb tsis ntev los no qhia tias PTRA (Percutaneous transluminal raum angioplasty) tej zaum yuav muab kev kho mob thiab cov txiaj ntsig kev tuag rau cov neeg mob uas muaj kev pheej hmoo siab, xws li cov neeg uas muaj lub ntsws pulmonary edema, refractory hypertension, los yog lub raum tsis ua haujlwm sai (Ritchie li al., 2014). Txawm li cas los xij, cov txheej txheem hauv qab muaj peev xwm rau lub raum tau txais txiaj ntsig los ntawm revascularization tseem tsis tau paub ntau.

RAS (lub raum hlab ntsha stenosis) tau muaj feem cuam tshuam nrog kev ua haujlwm thiab kev puas tsuaj ntawm mitochondria, uas nyob ib feem ntawm cytoplasmic ntim ntawm lub raum tubular hlwb los muab lub zog rau kev thauj mus los thiab tswj cellular homeostasis (McFarland li al., 2007; Pfaller & Rittinger, 1980).In swine RAS (lub raum hlab ntsha stenosis), lubpost-stenotic raumnthuav tawm mitochondrial kev puas tsuaj thiab kev ua haujlwm tsis zoo, cuam tshuam nrog lub raum hypoxia, oxidative stress, microvascular poob, fibrosis, thiab lub raum tsis ua haujlwm (Eirin et al., 2014; Eirin, Li, et al, 2012). Tsis tas li ntawd, superimposition ntawm MetS, uas yog txuam nrog rau lub raum tsis zoo tom qab PTRA(Percutaneous transluminal raum angioplasty)(Davies li al., 2010), ua kom pom kev puas tsuaj mitochondrial thiab lub raum tsis ua haujlwm hauv lub raum stenotic swine, cuam tshuam rau mitochondrial structural thiab functional alterations hauv pathogenesis ntawm RVD (Renovascular disease) (Nargesi, Zhang, et al., 20).

Nyob rau hauv txoj kev tshawb no tam sim no, peb coj kom zoo dua ntawm ib tug loj tsiaj qauv ntawm coexisting MetS thiab RAS (lub raum hlab ntsha stenosis) (Eirin li al., 2015) los tshawb txog qhov cuam tshuam ntawm lub raum revascularization ntawmpost-stenotic raummitochondria cov tsos mob. Peb kwv yees tias kev ruaj ntseg rau lub raum arterial patency nrog PTRA(Percutaneous transluminal raum angioplasty)Tej zaum yuav yog ib lub tswv yim zoo los khaws cov qauv mitochondrial thiab bioenergetics, thiab txo qis parenchymal raug mob thiab ua haujlwm tsis zoo hauv lub raum stenotic. Peb pom tias revascularization nce lub raum mitochondrial cov ntsiab lus (TOM-20 immunoreactivity) thiab attenuated, txawm tias tsis normalized, lub raum tubular cell thiab PTCEC mitochondrial o (tso qis mitochondrial cheeb tsam thiab perimeter) thiab cristae remodeling (nce matrix contrastity). podocyte mitochondrial cheeb tsam thiab perimeter tau sib npaug sib npaug hauv txhua pawg MetS, sib cav tawm tsam qhov cuam tshuam loj ntxiv ntawm RAS (lub raum hlab ntsha stenosis) ntawm cov duab podocyte mitochondrial, thiab podocyte mitochondrial matrix ntom ntom ua tsis tau zoo hauv MetS ntxiv RAS ntxiv rau PTRA.(Percutaneous transluminal raum angioplasty)npua. Txawm li cas los xij, PTRA(Percutaneous transluminal raum angioplasty)nce COX-IV kev ua haujlwm thiab ATP ntau lawm hauv lub raum mitochondria. Muab hais tias mitochondria yog lub hauv paus loj ntawm ATP hauv lub raum tubular hlwb, nws yuav muaj peev xwm nce mitochondrial ntom thiab attenuation ntawm lub raum tubular cell mitochondrial kev puas tsuaj tuaj yeem pab txhim kho mitochondrial bioenergetics hauv PTRA-kho npua. Xwb, amelioration ntawm lub raum mitochondrial H202 ntau lawm, uas ua rau ntau yam mitochondrial structural Cheebtsam thiab compromises ATP synthesis (Bao li al., 2009), yuav muaj ib feem pab txhim kho mitochondrial bioenergetics hauv MetS ntxiv RAS ntxiv rau PTRA npua.

Interestingly, txawm tias attenuation ntawm H202 ntau lawm, PTRA(Percutaneous transluminal raum angioplasty)ua tsis tiav los txhim kho lub raum oxidative kev nyuaj siab, raws li kev xav los ntawm kev nce hauv qhov chaw tsim khoom ntawm superoxide anion. Lub raum oxidative kev nyuaj siab ncaj qha cuam tshuam rau lub raum stenotic ncig ntawm ntau theem los ntawm cov ceg tseem ceeb ntawm lub raum cov hlab ntsha mus rau me me peritubular capillaries (Chade, 2013).ROS tuaj yeem ua raws li vasoconstrictors ncaj qha thiab tsim cov vasoactive thiab fibrogenic yam, txo qhov muaj nitric oxide, uas. nyiam tshaj plaws ntawm vasoconstrictors, xws li endothelin-1 lossis angiotensin-II (Zhu et al.2004a). Txawm li cas los xij, microvascular ntom ntom uas txo qis hauv MetS ntxiv rau RAS (lub raum hlab ntsha stenosis), txhim kho hauv PTRA.(Percutaneous transluminal raum angioplasty)-kho npua, zoo li lub nkoj loj hlob tuaj (xav txog hauv cov hlab ntsha tortuosity tsawg), qhia tias kev kho dua tshiab ntawm lub raum hlab ntsha patency txhim kho microvascular architecture hauv lub cev.post-stenotic raum. Tsis tas li ntawd, tus naj npawb ntawm peritubular capillaries uas txo qis hauv MetS ntxiv rau RAS (lub raum hlab ntsha stenosis) piv rau Lean thiab MetS, nce tom qab PTRA.(Percutaneous transluminal raum angioplasty), tej zaum vim yog kev khaws cia ntawm PTCEC mitochondrial morphology. Tseeb tiag, PTCEC mitochondrial cheeb tsam inversely correlated nrog cov naj npawb ntawm peritubular capillaries nyob rau hauv lub raum ischemic, txhawb kev xav tias preservation ntawm PTCEC mitochondria yuav pab tau rau ameliorate RVD (Renovascular disease)-vim lub raum vascular puas, Cov txiaj ntsig no yog nyob rau hauv txoj kab nrog peb yav dhau los. Kev soj ntsuam hauv swine RAS (lub raum hlab ntsha stenosis) uas cov tswv yim kho mob, xws li ntxiv nrog cov monocyte chemoattractant protein-I inhibitor binder nws, muaj peev xwm khaws cia lub raum microvasculature thiab lub raum ua haujlwm yam tsis muaj ntshav siab thiab vascular oxidative stress (Zhu li al., 2009).

PTRA(Percutaneous transluminal raum angioplasty)kuj txo qis tubular raug mob thiab txo tubulointerstitial fibrosis, tej zaum ib feem vim revascularization khaws cia raum tubular cell mitochondrial morphology thiab muaj nuj nqi. Qhov no zoo ib yam nrog peb cov kev soj ntsuam uas lub raum tubular cell mitochondrial matrix ceev thiab ATP tiam correlated inversely nrog post-stenotic tubular raug mob thiab tubulointerstitial fibrosis, feem. Txawm li cas los xij, tus naj npawb ntawm sclerotic glomeruli hauv lub raum stenotic tau zoo sib xws hauv MetS ntxiv rau RAS thiab MetS ntxiv RAS ntxiv rau PTRA npua, yuav yog ib feem vim lub raum revascularization ua tsis tau zoo los txhim kho podocyte mitochondrial morphology.

Qhov tseem ceeb, lub raum revascularization nce stenotic raum ntim, RBF, thiab GFR, thiab txo cov ntshav creatinine. Ob peb lub tswv yim yuav tau suav txog kev txhim kho ntawm RBF thiab GFR txawm hais tias muaj kev kub siab renovascular thiab cov qib zoo sib xws ntawm stenosis hauv peb txoj kev tshawb fawb, xws li kev tshem tawm cov kev taw qhia pro-fibrotic (Warner li al., 2012), uas tej zaum yuav tau khaws cia mitochondrial ua pa ( Dimeloe li al. 2019) thiab kev khaws cia ntawm lub raum cortical microvascular ntom, ib qho tseem ceeb txiav txim siab ntawm lub raum ua haujlwm hauv lub raum.post-stenotic raum(Chade, 2013). Interestingly, peb pom tias mitochondrial ntom correlated ncaj qha nrog stenotic-mob raum GFR, qhia tias kev khaws cia ntawm lub raum mitochondrial cov ntsiab lus yuav pab tau rau ib co degree los txhim kho lub raum ua hauj lwm tshaj li stenotic lesion. Txawm li cas los xij, BP tau zoo sib xws hauv MetS ntxiv rau RAS (lub raum hlab ntsha stenosis) pawg, tejzaum nws yog vim muaj kev nrhiav neeg ua haujlwm ntxiv, xws li ncig isoprostanes. Systemic isoprostanes yog cov khoom ntawm oxidation uas tuaj yeem ua rau cov lus teb tsis zoo ntawm cov hlab ntsha, ob qho tib si hauv vivo thiab hauv vitro. Infusion ntawm isoprostanes nyob rau hauv hypercholesterolemic npua nce arterial siab thiab oxidative kev nyuaj siab (Wilson li al., 1999). Cov vasoconstrictors muaj zog no kuj tseem cuam tshuam rau kev txhawb nqa kev mob ntshav siab renovascular (Lerman li al., 2001). Zoo ib yam li cov ntaub so ntswg ROS ntau lawm, PTRA(Percutaneous transluminal raum angioplasty)tsis txo qis isoprostane qib. Yog li ntawd, PTRA ua tsis tau tejyam rau attenuate ncaj qha los ntawm kev txhim kho rhiab heev rau vasoconstrictor isoprostanes los txhawb kev kub siab hauv MetS ntxiv rau RAS (lub raum hlab ntsha stenosis).

Zuag qhia tag nrho, txoj kev tshawb fawb tam sim no qhia txog cov txheej txheem tshiab uas PTRA(Percutaneous transluminal raum angioplasty)Tej zaum yuav muaj txiaj ntsig zoo hauv kev sib koom ua ke MetS thiab RAS (lub raum hlab ntsha stenosis). Peb tau pom yav dhau los hauv atherosclerotic RAS (lub raum hlab ntsha stenosis) uas PTRA(Percutaneous transluminal raum angioplasty)ua tsis tiav los txhim kho mitochondrial lossis lub raum ua haujlwm (Eirin li al., 2014). Kev soj ntsuam uas PTRA(Percutaneous transluminal raum angioplasty)zoo nkaus li nyob rau hauv lub sij hawm luv luv muaj txiaj ntsig zoo hauv MetS ntxiv rau RAS dua li hauv atherosclerotic RAS (lub raum hlab ntsha stenosis) yog qhov nthuav. Tsis zoo li RAS (lub raum hlab ntsha stenosis), MetS yog tus cwj pwm los ntawm lub raum ntim, RBF, thiab GFR piv rau Lean npua, yuav yog vim lawv lub cev hnyav dua thiab hyperfiltration (Einin li al., 2017; Pawar li al., 2015). Tej zaum, MetS-induced hyperfiltration nyob rau hauv cov qauv no yuav tau npog qhov hemodynamic cuam tshuam ntawm RAS ntawm stenotic raum mitochondrial qauv thiab kev ua haujlwm, paradoxically nyiam lawv cov lus teb rau lub raum revascularization. Txawm li cas los xij, nws yog ib qho tseem ceeb kom nco ntsoov tias PTRA(Percutaneous transluminal raum angioplasty)txhim kho, tab sis tsis normalized, ob lub raum thiab mitochondrial muaj nuj nqi. Tej zaum, kev kho mob mitoprotective adjuvant tuaj yeem siv cov txiaj ntsig ntxiv los khaws cov mitochondrial kev ncaj ncees thiab kev ua haujlwm hauv lub raum ischemic thiab ntxiv txhim kho lossis kho lub raum tom qab PTRA.(Percutaneous transluminal raum angioplasty). Kev ua tsis tiav ntawm lub raum ua haujlwm kuj txhais tau hais tias kev hloov pauv ntawm cov txheej txheem pathogenic ntxiv (xws li lub raum mob, kho vascular remodeling, thiab lwm yam) hauv MetS ntxiv rau RAS (lub raum hlab ntsha stenosis) yuav xav tau los kho lub raum stenotic.

Thaum kawg, txhawm rau txheeb xyuas lub luag haujlwm ntawm lub raum revascularization los tiv thaiv covpost-stenotic raum, peb piv cov teebmeem ntawm kev kho mob ntshav siab, cytoprotection, thiab PTRA(Percutaneous transluminal raum angioplasty)ntawm cov ntshav siab, lub raum hemodynamics, thiab kev raug mob hauv cov qauv npua (Table 3). Peb tau pom yav dhau los tias 4-lub lim tiam ntawm kev kho mob tus qauv nrog valsartan lossis triple therapy (reserpine, hydralazine, thiab hydrochlorothiazide) tom qab 10 lub lis piam ntawm swine unilateral RAS (lub raum hlab ntsha stenosis) txo cov ntshav siab, lub raum oxidative stress, thiab fibrosis, thiab txhim kho cov kab mob hauv lub raum microvasculature thiab angiogenesis (Zhang li al., 2013). Txawm li cas los xij, tsis muaj valsartan lossis triple therapy txhim kho stenotic-mob raum RBF thiab GFR, txhawb kev siv hluav taws xob ntawm PTRA.(Percutaneous transluminal raum angioplasty)txhawm rau txhim kho lub raum hemodynamics thiab ua haujlwm dhau ntawm qhov mob stenotic. Peb kuj tau pom yav dhau los hauv swine RAS (lub raum hlab ntsha stenosis) uas tom qab 4 lub lis piam ntawm kev kho mob nrog elamipretide (ELAM), mitochondria-targeted peptide uas khaws cov qauv mitochondrial thiab kev ua haujlwm,post-stenotic raumangiogenesis, microvascular density, RBF, thiab GFR txhim kho, thiab fibrosis txo qis (Eirin et al., 2014), Cov teebmeem salutary no zoo ib yam li cov kev soj ntsuam tam sim no hauv MetS ntxiv rau RAS ntxiv rau PTRA-kho npua. Yog li, kev puas tsuaj rau lub raum mitochondrial tuaj yeem ua lub luag haujlwm tseem ceeb hauv kev tsim cov kab mob ntawm lub raum raug mob thiab ua haujlwm tsis zoo thiab tuaj yeem yog qhov tseem ceeb ntawm kev txiav txim siab ntawm lub raum tom qab PTRA.(Percutaneous transluminal raum angioplasty).

Peb txoj kev tshawb fawb yog txwv los ntawm lub sijhawm luv luv ntawm tus kab mob thiab kev siv cov tsiaj me me, uas tej zaum yuav piav qhia txog qhov tsis sib xws ntawm lub raum tshwm sim tom qab PTRA.(Percutaneous transluminal raum angioplasty)piv rau tib neeg RVD (Renovascular disease). Txawm li cas los xij, peb tus qauv ua raws li kev sib koom ua ke ntawm RAS (lub raum hlab ntsha stenosis) thiab MetS cov khoom ntawm tib neeg RVD. Txawm hais tias PTRA(Percutaneous transluminal raum angioplasty)attenuated mitochondrial raug mob thiab txhim kho lub raum hemodynamics thiab ua hauj lwm nyob rau hauv lubpost-stenotic raum, nws tsis tuaj yeem txhim kho BP hauv 4 lub lis piam, zoo ib yam li kev soj ntsuam uas lub raum revascularization hauv tib neeg tsis tas li txo BP. Cov kev tshawb fawb yav tom ntej yog xav tau los tsim kom muaj kev pheej hmoo ntawm cov txiaj ntsig zoo ntawm PTRA(Percutaneous transluminal raum angioplasty)nyob rau hauv lub raum mitochondria nyob rau lub sij hawm ntev thiab nyob rau hauv tib neeg.

Hauv cov ntsiab lus, peb txoj kev tshawb fawb qhia tau hais tias lub raum revascularization txhim kho GFR thiab ameliorated tubular raug mob thiab tubulointerstitial fibrosis nyob rau hauv lub raum stenotic ntawm MetS ntxiv rau RAS (lub raum hlab ntsha stenosis) npua. Qhov no tau cuam tshuam nrog rau lub raum mitochondrial structural abnormalities thiab ROS ntau lawm thiab txhim kho bioenergetics. Tsis tas li ntawd, peb pom tias lub raum mitochondrial cov ntsiab lus, morphology, thiab kev ua haujlwm yuav yog qhov tseem ceeb rau kev txiav txim siab ntawm lub raum raug mob thiab ua haujlwm tsis zoo tom qab PTRA.(Percutaneous transluminal raum angioplasty). Yog li, peb txoj kev tshawb fawb qhia txog lub luag haujlwm tseem ceeb rau mitochondria hauv kev tswj hwm GFR thiab txo qis rau lub raum kev puas tsuaj hauv MetS ntxiv rau RAS (lub raum hlab ntsha stenosis) thiab txhawb kev tshawb nrhiav cov tswv yim mitoprotective los khaws cov qauv thiab kev ua haujlwm ntawm lub raum.post-stenotic raum. Cov kev tshawb fawb ntxiv yog xav tau kom paub meej tias qhov ua tau zoo ntawm PTRA(Percutaneous transluminal raum angioplasty)kom txo qis lub raum mitochondrial raug mob hauv kev sim MetS ntxiv rau RAS (lub raum hlab ntsha stenosis) thiab tib neeg RVD (Renovascular disease).


treatment for post-stenotic kidney

Cov ntaub ntawv

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Koj Tseem Yuav Zoo Li