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Spatial region-resolved proteome map reveals mechanism of COVID-19-associated heart injury
Ling Leng1, Jie Ma2, Pei-Pei Zhang3
1Stem Cell and Regenerative Medicine Lab, Department of Medical Science Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Translational Medicine Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
Insights
Direct inflammation from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes cardiac injury in COVID-19. This study maps heart inflammation, finding the left atrium most vulnerable, guiding cardiovascular disease treatments.
Area of Science:
- Cardiology
- Virology
- Proteomics
Background:
- Direct myocardial and vascular injuries from SARS-CoV-2 infection-driven inflammation are primary causes of COVID-19-associated acute cardiac injury.
- Detailed understanding of cardiac inflammation injury characteristics remains limited.
Purpose of the Study:
- To create a region-resolved proteome map of the myocardia and microvessels in COVID-19 patient hearts with inflammatory cell infiltration.
- To identify specific molecular dysfunctions in different cardiac regions due to SARS-CoV-2.
Main Methods:
- Quantitative spatial proteomics strategy.
- Comparative anatomy.
- Laser-capture microdissection.
- Histological examination.
Main Results:
- A region-resolved proteome map of cardiac myocardia and microvessels was established for COVID-19 hearts.
- Molecular dysfunctions were identified in myocardia and microvessels across different cardiac regions.
- The left atrial myocardia and microvessels demonstrated the highest susceptibility to SARS-CoV-2 infection and inflammatory storm.
Conclusions:
- The left atrium is the most vulnerable cardiac region to SARS-CoV-2-induced inflammation.
- Findings highlight the need for focused attention on left atrial lesions and treatment strategies.
- Results provide guidance for improving clinical management of COVID-19-related cardiovascular diseases.
Abstract:
Direct myocardial and vascular injuries due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-driven inflammation is the leading cause of acute cardiac injury associated with coronavirus disease 2019 (COVID-19). However, in-depth knowledge of the injury characteristics of the heart affected by inflammation is lacking. In this study, using a quantitative spatial proteomics strategy that combines comparative anatomy, laser-capture microdissection, and histological examination, we establish a region-resolved proteome map of the myocardia and microvessels with obvious inflammatory cells from hearts of patients with COVID-19. A series of molecular dysfunctions of myocardia and microvessels is observed in different cardiac regions. The myocardia and microvessels of the left atrial are the most susceptible to virus infection and inflammatory storm, suggesting more attention should be paid to the lesion and treatment of these two parts. These results can guide in improving clinical treatments for cardiovascular diseases associated with COVID-19.
