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Updated: Oct 29, 2025
In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model
Published on: October 27, 2020
Carbonic anhydrase IX and hypoxia-inducible factor 1 attenuate cardiac dysfunction after myocardial infarction
Mariela Beatriz Nolly1, Lorena Alejandra Vargas2, María Verónica Correa3
1Laboratorio de Bioquímica e Inmunidad, IMBECU-CONICET-UNCuyo, Instituto de Bioquímica y Biotecnología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, 5500, Mendoza, Argentina. mariela.nolly@gmail.com.
Insights
Hypoxia-inducible factor (HIF-1) activation in myocardial infarction (MI) boosts carbonic anhydrase IX (CAIX) and sodium bicarbonate transporter 1 (NBC1). This interaction protects heart tissue from acidic damage, improving cardiac function post-MI.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cellular Physiology
Background:
- Myocardial infarction (MI) significantly impacts global mortality, with infarct size and cardiac remodeling dictating prognosis and heart failure risk.
- Hypoxia-inducible factor 1 (HIF-1) activation in hypoxic regions post-MI is known to reduce infarct size and improve cardiac function.
- HIF-1 activation leads to the transcription of carbonic anhydrase IX (CAIX), an enzyme crucial for regulating intracellular pH in the heart.
Purpose of the Study:
- To investigate the role of carbonic anhydrase IX (CAIX) in cardiac remodeling following myocardial infarction (MI).
- To explore the relationship between CAIX, sodium bicarbonate transporter 1 (NBC1), and HIF-1 in the context of post-MI cardiac remodeling.
- To elucidate the potential protective mechanisms involving CAIX and NBC1 in hypoxic heart tissue.
Main Methods:
- Utilized an in vivo rat coronary artery ligation model to simulate myocardial infarction.
- Employed isolated cardiomyocytes subjected to hypoxic conditions for in vitro analysis.
- Applied immunohistochemistry, immunoblotting, confocal microscopy, and immunoprecipitation to assess protein expression and interactions.
Main Results:
- Increased HIF-1 levels were observed in infarcted cardiac tissue and hypoxic cardiomyocytes within 2 hours.
- Carbonic anhydrase IX (CAIX) expression and plasma membrane localization increased post-MI, particularly at 24 hours.
- Sodium bicarbonate transporter 1 (NBC1) expression rose in cardiac tissue after 2 hours of infarction, and CAIX-NBC1 interaction was enhanced in MI tissue.
Conclusions:
- CAIX interacts with NBC1 in the context of myocardial infarction, suggesting a protective mechanism against acidic damage in hypoxic cardiac tissue.
- This CAIX-NBC1 interaction represents a potential therapeutic target for mitigating adverse cardiac remodeling and improving outcomes after MI.
- The findings highlight the critical role of pH regulation via CAIX and NBC1 in preserving cardiac function during and after ischemic events.
Abstract:
Myocardial infarction (MI) is one of the leading causes of death worldwide. Prognosis and mortality rate are directly related to infarct size and post-infarction pathological heart remodeling, which can lead to heart failure. Hypoxic MI-affected areas increase the expression of hypoxia-inducible factor (HIF-1), inducing infarct size reduction and improving cardiac function. Hypoxia translocates HIF-1 to the nucleus, activating carbonic anhydrase IX (CAIX) transcription. CAIX regulates myocardial intracellular pH, critical for heart performance. Our objective was to investigate CAIX participation and relation with sodium bicarbonate transporters 1 (NBC1) and HIF-1 in cardiac remodeling after MI. We analyzed this pathway in an "in vivo" rat coronary artery ligation model and isolated cardiomyocytes maintained under hypoxia. Immunohistochemical studies revealed an increase in HIF-1 levels after 2 h of infarction. Similar results were observed in 2-h infarcted cardiac tissue (immunoblotting) and in hypoxic cardiomyocytes with a nuclear distribution (confocal microscopy). Immunohistochemical studies showed an increase CAIX in the infarcted area at 2 h, mainly distributed throughout the cell and localized in the plasma membrane at 24 h. Similar results were observed in 2 h in infarcted cardiac tissue (immunoblotting) and in hypoxic cardiomyocytes (confocal microscopy). NBC1 expression increased in cardiac tissue after 2 h of infarction (immunoblotting). CAIX and NBC1 interaction increases in cardiac tissue subjected to MI for 2h when CAIX is present (immunoprecipitation). These results suggest that CAIX interacts with NBC1 in our infarct model as a mechanism to prevent acidic damage in hypoxic tissue, making it a promising therapeutic target.
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