Dysregulated Calcium Handling in Cirrhotic Cardiomyopathy
Cirrhotic cardiomyopathy is a syndrome of blunted cardiac systolic and diastolic function in patients with cirrhosis. However, the mechanisms remain incompletely known. Since contractility and relaxation depend on cardiomyocyte calcium transients, any factors that impact cardiac contractile and rela...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/7/1895 |
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| author | Sang Youn Hwang Hongqun Liu Samuel S. Lee |
| author_facet | Sang Youn Hwang Hongqun Liu Samuel S. Lee |
| author_sort | Sang Youn Hwang |
| collection | DOAJ |
| description | Cirrhotic cardiomyopathy is a syndrome of blunted cardiac systolic and diastolic function in patients with cirrhosis. However, the mechanisms remain incompletely known. Since contractility and relaxation depend on cardiomyocyte calcium transients, any factors that impact cardiac contractile and relaxation functions act eventually through calcium transients. In addition, calcium transients play an important role in cardiac arrhythmias. The present review summarizes the calcium handling system and its role in cardiac function in cirrhotic cardiomyopathy and its mechanisms. The calcium handling system includes calcium channels on the sarcolemmal plasma membrane of cardiomyocytes, the intracellular calcium-regulatory apparatus, and pertinent proteins in the cytosol. L-type calcium channels, the main calcium channel in the plasma membrane of cardiomyocytes, are decreased in the cirrhotic heart, and the calcium current is decreased during the action potential both at baseline and under stimulation of beta-adrenergic receptors, which reduces the signal to calcium-induced calcium release. The study of sarcomere length fluctuations and calcium transients demonstrated that calcium leakage exists in cirrhotic cardiomyocytes, which decreases the amount of calcium storage in the sarcoplasmic reticulum (SR). The decreased storage of calcium in the SR underlies the reduced calcium released from the SR, which results in decreased cardiac contractility. Based on studies of heart failure with non-cirrhotic cardiomyopathy, it is believed that the calcium leakage is due to the destabilization of interdomain interactions (dispersion) of ryanodine receptors (RyRs). A similar dispersion of RyRs may also play an important role in reduced contractility. Multiple defects in calcium handling thus contribute to the pathogenesis of cirrhotic cardiomyopathy. |
| first_indexed | 2024-03-11T01:16:56Z |
| format | Article |
| id | doaj.art-b56c45d5be8b4ccca1759e2d8b52bd37 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T01:16:56Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj.art-b56c45d5be8b4ccca1759e2d8b52bd372023-11-18T18:26:31ZengMDPI AGBiomedicines2227-90592023-07-01117189510.3390/biomedicines11071895Dysregulated Calcium Handling in Cirrhotic CardiomyopathySang Youn Hwang0Hongqun Liu1Samuel S. Lee2Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, CanadaLiver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, CanadaLiver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, CanadaCirrhotic cardiomyopathy is a syndrome of blunted cardiac systolic and diastolic function in patients with cirrhosis. However, the mechanisms remain incompletely known. Since contractility and relaxation depend on cardiomyocyte calcium transients, any factors that impact cardiac contractile and relaxation functions act eventually through calcium transients. In addition, calcium transients play an important role in cardiac arrhythmias. The present review summarizes the calcium handling system and its role in cardiac function in cirrhotic cardiomyopathy and its mechanisms. The calcium handling system includes calcium channels on the sarcolemmal plasma membrane of cardiomyocytes, the intracellular calcium-regulatory apparatus, and pertinent proteins in the cytosol. L-type calcium channels, the main calcium channel in the plasma membrane of cardiomyocytes, are decreased in the cirrhotic heart, and the calcium current is decreased during the action potential both at baseline and under stimulation of beta-adrenergic receptors, which reduces the signal to calcium-induced calcium release. The study of sarcomere length fluctuations and calcium transients demonstrated that calcium leakage exists in cirrhotic cardiomyocytes, which decreases the amount of calcium storage in the sarcoplasmic reticulum (SR). The decreased storage of calcium in the SR underlies the reduced calcium released from the SR, which results in decreased cardiac contractility. Based on studies of heart failure with non-cirrhotic cardiomyopathy, it is believed that the calcium leakage is due to the destabilization of interdomain interactions (dispersion) of ryanodine receptors (RyRs). A similar dispersion of RyRs may also play an important role in reduced contractility. Multiple defects in calcium handling thus contribute to the pathogenesis of cirrhotic cardiomyopathy.https://www.mdpi.com/2227-9059/11/7/1895cirrhotic cardiomyopathyL-type calcium channelryanodine receptorscardiac contractilitycalcium transient |
| spellingShingle | Sang Youn Hwang Hongqun Liu Samuel S. Lee Dysregulated Calcium Handling in Cirrhotic Cardiomyopathy Biomedicines cirrhotic cardiomyopathy L-type calcium channel ryanodine receptors cardiac contractility calcium transient |
| title | Dysregulated Calcium Handling in Cirrhotic Cardiomyopathy |
| title_full | Dysregulated Calcium Handling in Cirrhotic Cardiomyopathy |
| title_fullStr | Dysregulated Calcium Handling in Cirrhotic Cardiomyopathy |
| title_full_unstemmed | Dysregulated Calcium Handling in Cirrhotic Cardiomyopathy |
| title_short | Dysregulated Calcium Handling in Cirrhotic Cardiomyopathy |
| title_sort | dysregulated calcium handling in cirrhotic cardiomyopathy |
| topic | cirrhotic cardiomyopathy L-type calcium channel ryanodine receptors cardiac contractility calcium transient |
| url | https://www.mdpi.com/2227-9059/11/7/1895 |
| work_keys_str_mv | AT sangyounhwang dysregulatedcalciumhandlingincirrhoticcardiomyopathy AT hongqunliu dysregulatedcalciumhandlingincirrhoticcardiomyopathy AT samuelslee dysregulatedcalciumhandlingincirrhoticcardiomyopathy |