Spatial region-resolved proteome map reveals mechanism of COVID-19-associated heart injury

Leng, Ling; Ma, Jing; Zhang, Peipei; Xu, Si-Chi; Li, Xiao; Jin, Ye; Cai, Jun; Tang, Rui; Zhao, Lei; He, Zhicheng; Li, Man-Sheng; Zhang, Hui; Zhou, Liangrui; Wu, Zhihong; Li, Tianran; Zhu, Yunping; Wang, Yujie; Wu, Haibo; Ping, Yi‐Fang; Yao, Xiaohong; Zhu, Chuhong; Guo, Hai-Tao; Tan, Le-Yong; Liang, Zhiyong; Bian, Xiu‐Wu; Zhang, Shuyang

doi:10.1016/j.celrep.2022.110955

Cited by 19 publications

(24 citation statements)

References 40 publications

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“…1). Adult samples, but not those from the elderly, had an induction of complement component C1S, the ATPase PSMC6, hemoglobin HBE1, and the metallo-protease CPN1 which have each been implicated in host response to SARS-CoV-2, COVID-19 severity, and/or have anti-viral activity [68][69][70][71][72][73] . Additionally, stimulated adult, but not elder, samples had reduced PPIA.…”

Section: Discussionmentioning

confidence: 99%

The mRNA vaccine BNT162b2 demonstrates impaired TH1 immunogenicity in human elders in vitro and aged mice in vivo

Brook

Fatou

Checkervarty

et al. 2022

Preprint

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mRNA vaccines have been key to addressing the SARS-CoV-2 pandemic but have impaired immunogenicity and durability in vulnerable older populations. We evaluated the mRNA vaccine BNT162b2 in human in vitro whole blood assays with supernatants from adult (18-50 years) and elder (≥60 years) participants measured by mass spectrometry and proximity extension assay proteomics. BNT162b2 induced increased expression of soluble proteins in adult blood (e.g., C1S, PSMC6, CPN1), but demonstrated reduced proteins in elder blood (e.g., TPM4, APOF, APOC2, CPN1, and PI16), including 30-85% lower induction of TH1-polarizing cytokines and chemokines (e.g., IFNγ, and CXCL10). Elder TH1 impairment was validated in mice in vivo and associated with impaired humoral and cellular immunogenicity. Our study demonstrates the utility of a human in vitro platform to model age-specific mRNA vaccine activity, highlights impaired TH1 immunogenicity in older adults, and provides rationale for developing enhanced mRNA vaccines with greater immunogenicity in vulnerable populations.

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Section: Discussionmentioning

confidence: 99%

The mRNA vaccine BNT162b2 demonstrates impaired TH1 immunogenicity in human elders in vitro and aged mice in vivo

Brook

Fatou

Checkervarty

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Microthrombosis can lead to endothelial dysfunction, which is considered a key contributor to the COVID-19 vasculopathy pathogenesis [69][70][71] . Leng et al [30] employed spatial region-resolved proteomics to conform whether the molecular function of microvessels in the myocardium infiltrated by monocytes or lymphocytes is damaged. They discovered that the proteins of acute inflammatory and innate immune responses were predominantly elevated in the cardiovascular system of patients with COVID-19, especially in the left atrium, indicating regionally specific injury, which is characteristic of microvessel damage following COVID-19 infection.…”

Section: Hypoxia-induced Cardiovascular Injury In Patients With Covid-19mentioning

confidence: 99%

“…Various pathological reports have identified SARS-CoV-2 viral proteins and genetic material in the CMs of patients with COVID-19 [16,26] . Furthermore, in vitro studies using human induced pluripotent stem cells (hiPSC) and isolated adult CMs as well as in vivo experiments using animal models confirm that SARS-CoV-2 infection occurs in CMs [27–30] . Collectively, these data support the hypothesis that COVID-19–associated myocardial injury can be caused by the direct infection of CMs and cardiotoxic defects in SARS-CoV-2.…”

Section: Sars-cov-2–induced Direct Myocardial Injurymentioning

confidence: 99%

Injury mechanism of COVID-19–induced cardiac complications

Leng

Bian

2023

Cardiology Plus

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Heart dysfunction is one of the most life-threatening organ dysfunctions caused by coronavirus disease 2019 (COVID-19). Myocardial or cardiovascular damage is the most common extrapulmonary organ complication in critically ill patients. Understanding the pathogenesis and pathological characteristics of myocardial and vascular injury is important for improving clinical diagnosis and treatment approach. Herein, the mechanism of direct damage caused by severe acute respiratory syndrome coronavirus 2 to the heart and secondary damage caused by virus-driven inflammation was reviewed. The pathological mechanism of ischemia and hypoxia due to microthrombosis and inflammatory injury as well as the injury mechanism of tissue inflammation and single myocardial cell necrosis triggered by the viral infection of pericytes or macrophages, hypoxia, and energy metabolism disorders were described. The latter can provide a novel diagnosis, treatment, and investigation strategy for heart dysfunctions caused by COVID-19 or the Omicron variant.

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“…In the whole human heart, the authors were able to locate calcified atherosclerotic plaques within the coronary arteries, extract specific regions of interest <1000 µm across, and quantify 1300 proteins from each region relating to pathways of cardiac muscle contraction, focal adhesion, blood coagulation, and plasminogen and platelet activation [60]. Similarly, laser microdissection coupled with MS identified over 2000 proteins in inflammatory microvessels and almost 2500 proteins in regions of inflamed myocardium from the left and right atria and ventricles of the human heart demonstrating region‐specific molecular responses in the heart following coronavirus‐19 infection [61]. Integration of omics strategies with three‐dimensional and imaging‐based platforms will likely be a valuable approach toward recapitulating the full complexity of biological systems in both health and disease.…”

Section: Proteomics Of the Heartmentioning

confidence: 99%

Multi‐omic analyses and network biology in cardiovascular disease

Reitz,

Kuzmanov,

Gramolini

2023

Proteomics

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Heart disease remains a leading cause of death in North America and worldwide. Despite advances in therapies, the chronic nature of cardiovascular diseases ultimately results in frequent hospitalizations and steady rates of mortality. Systems biology approaches have provided a new frontier toward unraveling the underlying mechanisms of cell, tissue, and organ dysfunction in disease. Mapping the complex networks of molecular functions across the genome, transcriptome, proteome, and metabolome has enormous potential to advance our understanding of cardiovascular disease, discover new disease biomarkers, and develop novel therapies. Computational workflows to interpret these data‐intensive analyses as well as integration between different levels of interrogation remain important challenges in the advancement and application of systems biology‐based analyses in cardiovascular research. This review will focus on summarizing the recent developments in network biology‐level profiling in the heart, with particular emphasis on modeling of human heart failure. We will provide new perspectives on integration between different levels of large “omics” datasets, including integration of gene regulatory networks, protein–protein interactions, signaling networks, and metabolic networks in the heart.

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Spatial region-resolved proteome map reveals mechanism of COVID-19-associated heart injury

Cited by 19 publications

References 40 publications

The mRNA vaccine BNT162b2 demonstrates impaired TH1 immunogenicity in human elders in vitro and aged mice in vivo

The mRNA vaccine BNT162b2 demonstrates impaired TH1 immunogenicity in human elders in vitro and aged mice in vivo

Injury mechanism of COVID-19–induced cardiac complications

Multi‐omic analyses and network biology in cardiovascular disease

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