Cov Calcium-regulating Hormones puas tuaj yeem cuam tshuam qhov cuam tshuam ntawm Pro-inflammatory kev puas tsuaj-txuas nrog cov qauv molecular hauv kev loj hlob ntawm lub plawv tsis ua haujlwm?

Xav paub ntau ntxiv plz hu raudavid.wan@wecistanche.com

TSAB NTAWV

Cov pov thawj loj hlob qhia txog lub luag haujlwm tseem ceeb ntawm cov tshuaj tiv thaiv kab mob hauv lub plawv tsis ua haujlwm (HF). Cov kev txhim kho tsis ntev los no hauv daim teb no qhia txog lub luag haujlwm tsis meej uas lub cev tiv thaiv kab mob hauv lub cev tiv thaiv kab mob HF. Cov hlwb puas lossis ntxhov siab, cardiomyocytes, tshwj xeeb, tso tawm cov qauv kev puas tsuaj cuam tshuam nrog cov qauv molecular (DAMPs) suav nrog HMGB1, S100 A8 / A9, HSP70, thiab lwm yam molecules, nthuav tawm cov txheej txheem paracrine uas ua rau lub cev tsis muaj zog. Tsim los ua ib qho kev hloov pauv, rov tsim dua tshiab, kev tiv thaiv hauv lub cev txawm li cas los xij yuav dhau los ua haujlwm dhau los thiab yog li ua rau kev txhim kho ntawm HF los ntawm kev hloov cov pacemaker atherosclerosis, contraction, thiab electromechanical coupling, txawm tias los ntawm impairing calcium homeostasis. Kev tshuaj xyuas tam sim no yuav tshawb txog qhov kev xav ntawm kev koom tes ntawm cov tshuaj calcium uas tswj hwm cov tshuaj xws li parathyroid hormone thiab parathyroid hormone-cov protein muaj feem cuam tshuam rau kev cuam tshuam qhov cuam tshuam ntawm ntau dhau ntawm DAMPs thiab yog li txhim kho cov yam ntxwv ntawm lub plawv, tshwj xeeb tshaj yog nyob rau theem mob. ntawm tus kab mob.

Nyem qhov no kom paub ntau ntxiv txog Cistanche

HEART Failure thiab inNNATE Immunity

Ntau yam kab mob plawv feem ntau ua rau muaj kev nyuaj siab, ntawm lub plawv tsis ua hauj lwm (HF). HF feem ntau cuam tshuam nrog ntau yam mob comorbid. Feem ntau rau cov kab mob xws li comorbidities yog kab mob, feem ntau cuam tshuam nrog oxidative kev nyuaj siab thiab endothelial dysfunction.1Qhov ntau yam ntawm cov kab mob plawv uas xaus rau hauv HF txawv heev nyob rau hauv lub sij hawm thiab qhov luaj li cas ntawm kev tiv thaiv kab mob. Yog li, kev raug mob ischemic, kub siab, thiab ntau yam kab mob metabolic, nrog rau kev mob plawv hauv lub cev, lub cev tsis ua haujlwm, thiab aortic stenosis yog tus cwj pwm los ntawm cov lus teb thib ob ntawm lub cev tiv thaiv kab mob, thaum myocarditis ntawm txawv keeb kwm, autoimmune thiab kis kab mob ( kab mob thiab kab mob) ua rau lub hauv paus ua kom lub hauv paus thiab yoog rawskev tiv thaiv kab mob.2Cov yam ntxwv tshwj xeeb ntawm kev tiv thaiv kab mob hauv HF tshwm sim los ntawm kev sib txawv etiological ua rau muaj kev sib tham dav hauv cov ntaub ntawv thiab nthuav tawm hauv ntau qhov kev tshuaj xyuas zoo.3–5Txog thaum tsis ntev los no, nws tau txiav txim siab tias cov leeg mob plawv, cov ntaub so ntswg sib txawv heev, muaj qhov txwv tsis pub muaj peev xwm rov tsim dua tshiab.Txawm li cas los xij, nws tau pom tias cov ntaub so ntswg raug mob tuaj yeem ua rau kev ua kom lub cev tsis muaj zog, thiab cov txheej txheem rov ua dua tshiab hauv myocardium.Pib raws li kev hloov kho cov tshuaj tiv thaiv txhawm rau kho cov ntaub so ntswg puas ntsoog, cov txheej txheem inflammatory yuav, txawm li cas los xij, nyob rau hauv qee qhov xwm txheej hloov mus rau hauv cov txheej txheem ntev uas ua rau muaj kev loj hlob ntawm lub plawv tsis ua haujlwm.

Yog hais tias, nyob rau hauv thawj zaug, mob heev theem ntawm kev raug mob, lub cev tiv thaiv kab mob (feem ntau innate) cov lus teb aiming ntawm cov ntaub so ntswg kho yog kho los ntawm feem ntau cov neeg nyob thiab infiltrating lub cev tiv thaiv kab mob, tom qab nyob rau hauv lub sij hawm ntev ntawm tus kab mob lub tswb ceeb toom tso tawm los ntawm cov stressed los yog puas hlwb pib lub nthwv dej thib ob ntawm lub cev tiv thaiv kab mob.4Lub plawv cov ntaub so ntswg qhia tag nrho cov tseem ceeb Cheebtsam ntawm lub teeb liab transduction system lub luag hauj lwm rau lub innate kev tiv thaiv nyob rau hauv lub plawv cov ntaub so ntswg.Lawv tuaj yeem qhib tau los ntawm ob qho tib si lub tswb ceeb toom exogenous thiab endogenous, cov kab mob cuam tshuam nrog cov qauv molecular (PAMPs), thiab kev puas tsuaj cuam tshuam nrog cov qauv molecular (DAMPs).Whereas PAMPs muaj exogenous, uas yog, kab mob los yog kab mob, keeb kwm (xws li cov khoom ntawm cov kab mob phab ntsa, lipopolysaccharides (LPS)), DAMPs yog endogenous molecules, feem ntau ntawm cov uas muaj qhov tseem ceeb, tsis muaj kev tiv thaiv kab mob intracellular zog.Cov tswv cuab tseem ceeb ntawm cov pab pawg no yog cov pab pawg neeg siab tshaj plaws lub thawv 1 (HMGB1), ib qho kev sib koom ua ke ntawm cov chromatin complex nrog ntau yam kev tswj hwm, molecular chaperone HSP70, cytokine S100 A8 / A9, thiab lwm yam. 6 7 Kev tso tawm ntawm cov molecules los ntawm lubpuas hlwb mus rau hauv qhov chaw extracellular / ncig qhib lub cuab yeej tiv thaiv ntawmkev tiv thaiv innate nyob rau hauv ntau yam ntaub so ntswg nyob rau hauv ib tug paracrine los yog endocrine zam. Mechanistically, nws tshwm sim los ntawm kev sib cuam tshuam ntawm DAMPs nrog ib pab pawg ntawm cov qauv kev lees paub receptors (PRRs), uas feem ntau yog tsev neeg ntawm tus xov tooj hu ua receptors (TLR) nrog TLR4 ua tus tswv cuab tseem ceeb, thiab tseem yog tus neeg txais kev pabcuam rau qib siab. glycation kawg khoom (RAGE).8 9Lub cev loj hlob ntawm cov pov thawj qhia txog qhov tseem ceeb ntawm cov molecules no rau kev loj hlob ntawm kev mob ntev hauv HF. Kev ua kom PRRs los ntawm HMGB1 thiab lwm yam DAMPs nyob rau theem mob ntawm cov ntaub so ntswg mob plawv tau pom tias muaj txiaj ntsig zoo tshaj plaws, cyto- tiv thaiv kev cuam tshuam (saib hauv Mann10). Piv txwv li, kev tswj xyuas mob hnyav ntawm HMGB1 mus rau hauv thaj chaw peri-infarction (tus qauv nas) kho qhov kev tsim kho ntawm cov ntaub so ntswg inducing proliferation thiab txawv ntawm cardiomyocytes.11 Ib yam li ntawd, overexpression ntawm HMGB1 nyob rau hauv transgenic nas txo necrosis thiab tag nrho infarct loj tom qab myocardial infarct. 12Nyob rau tib lub sijhawm, kev cuam tshuam ntev ntawm DAMPs yog qhov tsis zoo.13 Indirect pov thawj ntawm qhov ntawd yog qhov txo qis HMGB1 qib ntawm kev rov qab los ntawm cov ntshav muab rau cov ischemic cardiomyocytes whereas qhov inhibition ntawm HMGB1 tso tawm ntau dampens lub zog ntawm lub cev tiv thaiv kab mob.13 Hauv cov neeg mob uas muaj HF, qhov nce HMGB1 qib tau pom muaj feem cuam tshuam nrog tus kab mob hnyav.14–18 Kev nce ntshav ntawm HMGB1 hauv sepsis ua rau muaj qhov tsis zoo inotropic.19Qhov no kuj tau pom nyob rau hauv ntau yam tsiaj qauv ntawm cov kab mob plawv. Yog li, inhibition ntawm HMGB1 accelerates cardiomyocyte re-modeling nyob rau hauv cov nas qauv ntawm induced ischemic raug mob.20 Kev tswj hwm ntawm heranilheranilace-tone, ib qho tshwj xeeb HMGB1 inhibitor, ua rau txo qis hauv cheeb tsam infarction thiab txo qis lactate dehydrogenase thiab creatine kinase theem hauv myocardium. 21 Kev kho mob ntawm cov nas qus nrog recombinant HMGB1 nce qhov infarct loj murine qauv ntawm I/R raug mob.22

DAIM NTAWV THOV THIAB KEV PAB CUAM TSHUAJ TSHAJ PLAWS HAUV MYOCARDIUM

Cov txheej txheem molecular ntawm HMGB1 cov teebmeem yog qhov nyuaj heev, nyob ntawm lub xeev redox ntawm HMGB1, cov receptors nws cuam tshuam nrog, thiab, qhov tseem ceeb tshaj plaws, cov ntaub so ntswg effector. Txawm li cas los xij, nws tau lees paub tias nyob rau hauv feem ntau cov ntaub so ntswg nrog rau myocardium, HMGB1- ua rau lub teeb liab hloov txoj hauv kev pib nrog kev cuam tshuam nrog PRRs nrog cov nram qab no ua kom NF- nuclear receptor.23 Lub tom kawg transactivates txhawb nqa ntawm ntau cov noob, tshwj xeeb tshaj yog cov pro-inflammatory cytokines thiab chemokines. Txawm li cas los xij, ntxiv rau cov teebmeem ntawm HMGB1, nws zoo nkaus li tias hauv plawv cov leeg HMGB1 kuj tuaj yeem cuam tshuam nrog kev ua haujlwm tseem ceeb ntawm cardiomyocytes, uas yog nyob ntawm feem ntau ntawm cov txheej txheem nruj calcium homeostasis. Calcium tam sim no yog qhov tseem ceeb tshaj plaws rau kev tsim cov peev txheej ua haujlwm hauv lub plawv dhia-tsim myocytes, rau theem toj siab ntawm lub peev xwm ua haujlwm, thiab thaum kawg rau lub plawv excitation-contraction coupling.24-26 Yog li ntawd, kev puas tsuaj ntawm calcium homeostasis. yuav induce los yog aggravate txoj kev loj hlob ntawmPiv txwv li, mob plawv pathology.27 Hypocalcemia, piv txwv li, tej zaum yuav underlies lub etiology ntawm cardiomyopathies thiab HF whereas hypercalcemia ua rau calcification ntawm lub plawv li qub, thiab cov hlab ntsha ua rau myocardium fibrosis.28–30.Nws zoo nkaus li tias DAMPs tuaj yeem cuam tshuam nrog calcium homeostasis hauv cov leeg nqaij. Yog li, ligand-mediated activation ntawm ib pawg neeg hu xov tooj zoo li receptors nyob rau hauv murine tag nrho lub plawv thiab cardiomyocytes nyob rau hauv parallel nrog cov inflammatory teb (qhia ntawm IL6, ntau yam chemokines) kuj txuam nrog txo cardiomyocyte contractility.31 Nyob rau hauv vitro kev kho mob ntawm cais feline. plawv myocytes nrog HMGB1 ua rau 70 feem pua ​​​​ntawm cov sarcomere shortening thiab 50 feem pua ​​​​ntawm qhov siab ntawm lub ncov Ca2 ntxiv rau ib ntus. Nws tau txiav txim siab tias HMGB1 qhov tsis zoo inotropic cuam tshuam yog tshwm sim los ntawm kev txo cov calcium uas muaj nyob hauv plawv myocytes ntawm kev hloov pauv ntawm daim nyias nyias.calcium influx.32Nws kuj tseem pom tau tias HMGB1 nce qhov zaus ntawm Ca2 ntxiv rau lub txim, txo cov sarcoplasmic reticulum (SR) Ca2 ntxiv rau cov ntsiab lus, thiab txo qhov amplitude ntawm systolic Ca2 ntxiv rau ncua sij hawm thiab myocyte contractility (tsis zoo inotropic nyhuv) nyob rau hauv ib koob tshuaj-nyob ntawm tus neeg laus. rat ventricular myocytes.33 Cov kws sau ntawv qhia tias cov teebmeem no tau txuas nrog yav dhau los ua qauv qhia HMGB1/TLR4- nyob ntawm kev ua haujlwm ntawm NAD(P)H oxidase thiab ntau dua cov pa oxygen (ROS) ntau lawm nrog kev hloov kho redox ntawm lub plawv. ryanodine receptor (RyR2). Cov tom kawg tau paub tias ua lub luag haujlwm tseem ceeb hauv plawv excitation-contraction coupling los ntawm gating Ca2 ntxiv tso tawm los ntawm SR. Tsis tas li ntawd, oxidative kev nyuaj siab kuj tau pom tias ua kom Ca2 ntxiv / calmodulin-dependent protein kinase II los ntawm oxidizing cov enzyme thiab thiaj li ua rau RyR kev ua. Zuag qhia tag nrho, cov kws sau ntawv xaus lus tias qhov ROS-dependent HMGB1 cuam tshuam rau calcium to thiab yog li ntawm kev cog lus yuav ua rau muaj ntau yam pathologies ua rau HF.33.HMGB1 kuj tseem tuaj yeem tswj hwm hauv nas plawv myocytes ntawm LPS kev tswj hwm, nrog rau qhov txo qis hauv plawv ua haujlwm. HMGB1 qhov tshwj xeeb ntawm cov nyhuv no tau lees paub los ntawm kev sib xyaw nrog HMGB1 recombinant nrog cov txiaj ntsig tsis zoo inotropic ntawm sab laug ventricle.34Interestingly, qhov incubation ntawm tsis tau lwm DAMP, HSP70, nrog rau cov thawj nas cardiomyocytes kuj ua rau txo qis ntawm contractility; Txawm li cas los xij, cov kws sau ntawv txuas qhov no nrog NF-k-kev kho kom haum xeeb ntawm cov kws kho mob uas muaj kev sib haum xeeb thiab yog li nrog cov kab mob cardiomyocyte es tsis yog hloov pauv calcium homeostasis.3

CALCIUM-REGULATING FACTORS THIAB CARDIOVASCULAR DISEASES

Dab tsi yog qhov tseem ceeb ntawm kev tswj hwm calcium homeostasis thiab lawv puas muaj feem cuam tshuam nrog kev tiv thaiv kab mob hauv lub cev-kho cov calcium uas cuam tshuam? Cov qib calcium hauv cov ntshav yog tswj hwm feem ntau los ntawm calcium-regulating hormonal system uas suav nrog parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrP), vitamin D, thiab calcitonin. Lub hom phiaj tseem ceeb ntawm lub cev rau tag nrho cov tshuaj hormones / vitamin no yog lub raum, pob txha pob txha, thiab plab hnyuv. PTH, PTHrP, thiab vitamin D txhawb kev nce hauv cov ntshav calcium ntau ntau, thaum calcitonin muaj qhov cuam tshuam.35Vim lawv lub luag haujlwm tseem ceeb hauv calcium homeostasis, cov txheej txheem ntawm kev txiav txim ntawm calcium-regulating hormones tau kawm feem ntau hauv daim ntawv thov rau pob txha physiology. Txawm li cas los xij, PTH / PTHrP cov teebmeem kuj tau sau tseg rau ntau lub cev thiab cov ntaub so ntswg nrog rau lub plawv.PTH, nrog rau PTHrP, suav hais tias feem ntau yog cardio-tiv thaiv vim lawv pab txhawb kev nce hauv lub plawv dhia, zoo inotropic thiab chronotropic cuam tshuam, thiab coronary vasodilation.36-41 Txaus siab, peb cov ntaub ntawv tsis tau tshaj tawm qhia tau nce qib ntawm kev ncig PTH hauv cov neeg mob cardio. -myopathies, thiab qhov kev hloov pauv no cuam tshuam nrog qib siab ntawm HMGB1.Txawm hais tias PTH-kho hloov pauv hauv cov ntshav calcium uas cuam tshuam ncaj qha cuam tshuam rau lub plawv ua haujlwm, cov pov thawj loj hlob kuj qhia tau hais tias PTH / PTHrP ncaj qha cuam tshuam rau cardiomyocytes (Palmeri thiab Walker42 thiab cov ntaub ntawv muaj nyob hauv). Qhov no tau txhawb nqa los ntawm kev tshawb pom ntawm PTH / PTHrP receptor, PTH1R, qhia hauv cardiomyocytes. Yog li, mRNA ntawm PTH1R tau kuaj pom nyob rau hauv nas lub plawv cov ntaub so ntswg thiab kuj nyob rau hauv tib neeg ventricular myocytes, uas zoo nkaus li tau nce siab tom qab ischemic raug mob.43 44Cov teebmeem inotropic zoo ntawm PTH hauv cardiomyocytes yog kho los ntawm PTH1R thiab txuam nrog G-proteins nrog kev ua kom cov L-type calcium channels uas ua rau kom cov calcium intracellular.45-47 Chronotropic teebmeem tau pom tias yog nyob ntawm kev ua kom cov adenylate cyclase thiab downstream cAMP. signaling uas nce lubKuv f pacemaker tam sim no, tshwj xeeb tshaj yog nyob rau hauv lub sinoatrial node ntawm lub plawv.48 49Cov ntsiab lus ntawm calcium-regulating zog ntawm PTH / PTHrP system thiab calcium dysregulation nrog rau overactivation ntawm lub cev tiv thaiv kab mob nyob rau hauv lub chav kawm ntawm ntau yam mob plawv, nws muaj peev xwm hypothesized hais tias lub presumed cardioprotective yam ntxwv ntawm calcium-regulating cov tshuaj hormones. tuaj yeem ua lub luag haujlwm tseem ceeb hauv kev rov ua haujlwm ntawm lub plawv cov leeg.

CALCIUM-REGULATING HORMONES THIAB OVERACTIVATED INNATE Immune teb hauv plawv

Ntawm ntau yam calcium-regulating yam, PTHrP zoo nkaus li yog qhov nthuav tshaj tus neeg sib tw molecule. Tsis zoo li PTH, PTHrP tsis zais los ntawm lub caj pas parathyroid; Txawm li cas los xij, nws tau nthuav tawm thiab tso tawm hauv / los ntawm ntau hom cell sib txawv raws li lub cev thiab cov kab mob pathological thiab ntseeg tau tias ua raws li feem ntau paracrine lossis autocrine yam.50 Txawm hais tias lub cev kev ua haujlwm ntawm PTHrP tsis nkag siab tag nrho, cov txheej txheem molecular tseem ceeb. ntawm nws qhov kev ua zoo li, yam tsawg kawg hauv ib feem, PTH, vim tias ob qho tib si cov tshuaj hormones yog activating ligands ntawm PTH1R,51 ib tug G-protein coupled receptor uas muaj peev xwm qhib tau ob qho tib si adenyl cyclase thiab phospholipase C nrog pib ntawm lub teeb liab transduction txoj kev culminating nyob rau hauv cov lus qhia. ntawm ntau lub hom phiaj genes.52 PTHrP-mediated activation ntawm phospholipase C ua rau tsim inositol 1,4,5-trisphosphate (IP3) uas pib tso calcium los ntawm endoplasmic reticulum. PTHrP yog tib qho tshuaj calcium uas tswj hwm cov tshuaj hauv lub plawv. PTHrP protein tau kuaj pom nyob rau hauv ob qho tib si kev loj hlob thiab cov neeg laus lub siab lub ntsws.atrial myocytes.55 Txawm li cas los xij, nws kuj tau kuaj pom hauv ventricular cardiomyocytes.56Ua haujlwm tau zoo, PTHrP tau pom zoo los ua tus txheej txheem tswj hwm cov txheej txheem uas koom nrog kev tswj hwm ntawm vascular tone (thiab yog li ntshav siab), chronotropic, thiab inotropy, ua rau lub tswv yim ntawm PTHrP ua ib qho endocrine cardioprotective "txias mimetic". {1}}Tseeb tiag, nws cov lus qhia tau pom tias raug ntxias nyob rau hauv ischemic raug mob56 thiab congestive plawv tsis ua hauj lwm, 54, thiab contractile muaj nuj nqi ntawm stunned myocardium nyob rau hauv nas thiab npua tau txhim kho nyob rau hauv kev tswj ntawm recombinant PTHrP.58 Ib yam li ntawd, PTHrP txhim kho lub contractile teb ntawm cov neeg laus. rat cardiomyocytes.59Raws li tau pom yav dhau los, cov tshuaj tiv thaiv kab mob ntawm ntau yam mob plawv yog, tsawg kawg hauv ib feem, lub luag haujlwm rau kev ua haujlwm tsis zoo ntawm calcium homeostasis, uas ua rau nws ntxias kom xav tias qhov kev hloov kho mob hnyav tuaj yeem suav nrog kev cuam tshuam ntawm PTHrP los kho cov haujlwm ua haujlwm. ntawm cardiomyocytes.

Dab tsi yog cov pov thawj txhawb qhov kev xav no? Kev ua kom lub cev tiv thaiv kab mob raws li kev tsav tsheb los ntawm LPS tau pom tias yuav ua rau muaj mRNA ntawm PTHrP hauv cov kab mob sib txawv, suav nrog lub plawv, tom qab kev nthuav qhia hauv zos ntawm pro-inflammatory cytokines, TNF-, thiab IL-1. Nws tau hais tias lub zos paracrine lossis autocrine kev ua ntawm cov cytokines no yuav yog lub luag haujlwm rau qhov inducible PTHrP qhia thaum lub sij hawm tus tswv teb.60 Lwm qhov piv txwv ntawm cytokine-induced PTHrP over-expression tau pom nyob rau hauv nas mesangial hlwb. Nws tau pom tias PTHrP tuaj yeem ua qhov tseem ceeb ntawm kev ciaj sia los ntawm kev tawm tswv yim tsis zoo lub voj voog uas suav nrog kev txhim kho ntawm cyclooxygenase-2.61 Ntxiv mus, PTHrP noob qhia tuaj yeem qhib los ntawm NF-, uas yog lub ntsiab lus tseem ceeb ntawm cov receptors. orchestrating ntau yam downstream teebmeem ntawm DAMPs. Yog li, nws tau pom tias ib qho ntawm ob qhov sib txawv PTHrP gene promoters, P2, muaj NF- khi qhov chaw. Chromatin immunoprecipitation assays tau lees paub qhov kev sib khi hauv vivo ntawm p50 thiab c-Rel subunits ntawm NF- rau P2 txhawb nqa thaum tus kws tshaj xov xwm gene qhia tau pom NF--tsav kev tswj hwm ntawm P2 txhawb nqa ntawm PTHrP.62A cov qauv zoo li no. teeb liab transduction txoj kev culminating nyob rau hauv lub transcriptional gene activation/repression yog ib tug nruj me ntsis txwv lub sij hawm lub qhov rais, uas feem ntau yog tswj los ntawm cov tsis zoo tswv yim loops.63 Qhov no yog ib tug evolutionarily conserved mechanism uas tiv thaiv tshaj-sau ntawm lub hom phiaj cov khoom lag luam uas feem ntau yuav muaj ib tug detrimental cuam tshuam rau lub cev ntawm tes physiology. Immune-mediated upregulation of PTHrP qhia nyob rau hauv lub plawv zoo nkaus li ua raws li cov qauv ntawm lub cev, piv txwv li, PTHrP mRNA qib siab tshaj 1-2 teev tom qab txhaj tshuaj endotoxin nrog rov qab mus rau theem pib.60 Ntxiv mus, qhov cuam tshuam ntawm intracellular downstream ntawm PTHrP zoo ib yam li luv luv. 50 Tag nrho cov ntaub ntawv no hais txog kev pom zoo ntawm qhov kev xav tias ib qho ntawm qhov tshwm sim ntawm lub cev tiv thaiv kab mob ntau dhau- ntawm lub plawv pathologies tuaj yeem yog qhov cuam tshuam ntawm PTHrP qhia ua rau muaj kev cuam tshuam ntawm intracellular uas yuav txwv tsis pub muaj kev cuam tshuam ntawm ntau yam kev tiv thaiv kab mob xws li raws li PAMPs thiab DAMPs ntawm calcium homeostasis thiab yog li ntawd rov ua dua cov khoom cog lus ntawm cardiomyocytes. Nws tseem tuaj yeem pom tias yog vim li casrau cov qauv ntawm lub cev tshwj xeeb ntawm PTHrP-initiated signaling cascade, cov teebmeem cardioprotective tuaj yeem ua lub luag haujlwm tseem ceeb hauv cov theem pib (mob) ntawm kev tiv thaiv kab mob plawv. Muab cov ntaub ntawv muaj txiaj ntsig zoo los txhawb qhov kev xav no, nws yeej tsim nyog ntxiv cov kev tshawb fawb nruj uas tuaj yeem pab txhim kho cov kev kho tshiab uas siv cov calcium-regulating yam rau prophylaxis thiab / los yog kev kho mob ntawm lub cev tiv thaiv kab mob ntawm lub plawv tsis ua hauj lwm.