Cardiomyocyte Non-autonomous Factors and Cardiac Regeneration in Large Mammals
Cardiomyocyte Non-autonomous Factors and Cardiac Regeneration in Large Mammals
批准号:
10680563
负责人:
Wuqiang Zhu
金额:
$66.8万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
未结题
起止时间:
2022-08-09 至 2027-06-30
关键词:
AddressAdhesivesAdultAngiogenic FactorAntibodiesBiocompatible MaterialsBirthBlood VesselsBlood flowCardiacCardiac MyocytesCardiac Surgery proceduresCase StudyCell CycleCell SurvivalCellsChemicalsClinical ResearchCoculture TechniquesDataEmbryoEndothelial CellsEndotheliumFDA approvedFamily suidaeFishesFunctional disorderFutureGanglionectomyGenerationsGrowthHeartHeart InjuriesHumanHydrogelsInjuryInterventionLinkMaintenanceMammalsMapsMediatingModelingMusMyocardialMyocardial InfarctionMyocardial IschemiaMyocardiumNatural regenerationNeonatalNerve Growth FactorsNeuregulin 1NeuronsNewborn InfantNutrientOperative Surgical ProceduresPatientsPeripheralProliferatingProteomicsPublicationsRadionuclide ImagingRecombinantsRegenerative capacityRegenerative responseReportingResearchRodentRoleSignal PathwaySmooth Muscle MyocytesStressTestingTherapeuticTherapeutic InterventionVagotomyVascular Endothelial CellVascular Endothelial Growth FactorsVascularizationVentricularVertebratesZebrafishangiogenesisbevacizumabcardiac regenerationcardiogenesiscongenital heart disordercytokineenhancing factorexperimental studyfetalheart innervationinduced pluripotent stem cell derived cardiomyocytesischemic injurymouse modelnanoparticle deliveryneonatal micenerve supplyneuralneural networkneurotrophic factornovelparacrinepharmacologicpostnatalregeneration potentialresponsesingle-cell RNA sequencingultrasound
中文摘要
项目总结
英文摘要
Project Summary
In contrast to the cardiomyocytes (CMs) from lower vertebrates, adult mammalian CMs possess very limited
regenerative potential as a result of cell cycle exit. Interestingly, neonatal mice retain cardiac regenerative
capacity, which is lost by postnatal day 7. We have recently shown that 1-day-old pigs can also regenerate lost
myocardium in response to myocardial infarction (MI). This regeneration is mediated by the proliferation of
preexisting CMs, which does not occur when CMs permanently exit the cell cycle. Mechanisms underlying the
injury-mounted regenerative response especially in large mammals are not fully understood. However,
investigating underlying mechanisms is likely to identify novel targets for future therapeutic interventions.
Recent studies in fish and rodents emphasized the critical importance of vascularization and autonomic
innervation of the regenerating myocardium in zebrafish and neonatal mouse hearts. Besides their function to
provide nutrients, transport metabolites and enable adaptation to stress, it is unknown whether vascular and
neuronal cells, via paracrine interactions, also promote CM proliferation. Intriguingly, our preliminary data
support the idea that soluble factors, e.g., cytokines, secreted from vascular endothelial cells and peripheral
sympathetic neurons significantly stimulate cell cycle activity of co-cultured human induced pluripotent stem
cells-derived CMs, suggesting a critical role of nonmyocyte-CM interactions in modulating CM proliferation in
hearts of larger mammals post injury. In this project, we will exploit the established high regenerative capacity
of the neonatal pig heart model to experimentally address the role of nonmyocytes in injury-induced cardiac
regeneration in large mammals. Two specific aims are proposed. Aim 1 is to define the role of early
revascularization in injury-mounted cardiac regeneration. We will test the hypothesis that early
revascularization is essential for cardiac regeneration in neonatal pigs, and determine whether angiogenesis
promotes cardiac regeneration through the release of pro-myogenic factors from endothelial and/or smooth
muscle cells and/or via de novo formation of functional vessels for maintenance of CM viability. Aim 2 is to
delineate the role of autonomic innervation in injury-mounted cardiac regeneration. We will test the
hypothesis that innervation is essential for post injury cardiac regeneration in neonatal pigs, and determine if
biomaterial-mediated epicardial delivery of angiogenic and neurotrophic factors enhances cardiac regeneration
in neonatal pigs post MI.
期刊论文(3)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1007/s40291-022-00625-y
发表时间:
2023-03
期刊:
MOLECULAR DIAGNOSIS & THERAPY
影响因子:
4
作者:
[Son, Yura, Zhu, Wuqiang]
通讯作者:
Zhu, Wuqiang
DOI:
10.3390/biology13010047
发表时间:
2024-01-16
期刊:
Biology
影响因子:
4.2
作者:
[]
通讯作者:
Gastroenteropancreatic Neuroendocrine Tumor Metastasis to the Heart: Evaluation of Imaging Manifestations.
胃肠道神经内分泌肿瘤转移到心脏:成像表现的评估。
DOI:
10.1067/j.cpradiol.2022.11.011
发表时间:
2023-09
期刊:
CURRENT PROBLEMS IN DIAGNOSTIC RADIOLOGY
影响因子:
1.4
作者:
[Wang, Yuxiang, Ayoub, Chadi, Yang, Aaron F., Sonbol, Mohamad B., Butter, Richard, Halfdanarson, Thorvardur R., Arsanjani, Reza, Zhu, Wuqiang, Yang, Ming]
通讯作者:
Yang, Ming
Cardiomyocyte Non-autonomous Factors and Cardiac Regeneration in Large Mammals
-
批准号:10515862
-
项目类别:
-
资助金额:$68.45万
-
财政年份:2022
-
负责人:Wuqiang Zhu
-
依托单位:
Myocardial Repair with a Novel Engineered Cardiac Muscle Patch
-
批准号:10229464
-
项目类别:
-
资助金额:$41.28万
-
财政年份:2019
-
负责人:Wuqiang Zhu
-
依托单位:
Myocardial Repair with a Novel Engineered Cardiac Muscle Patch
-
批准号:10471216
-
项目类别:
-
资助金额:$41.28万
-
财政年份:2019
-
负责人:Wuqiang Zhu
-
依托单位:
Myocardial Repair with a Novel Engineered Cardiac Muscle Patch
-
批准号:10002275
-
项目类别:
-
资助金额:$41.73万
-
财政年份:2019
-
负责人:Wuqiang Zhu
-
依托单位:
海外基金