Metabolic Acidosis Results in Sexually Dimorphic Response in the Heart Tissue
Metabolic acidosis (MA) is a highly prevalent disorder in a significant proportion of the population, resulting from imbalance in blood pH homeostasis. The heart, being an organ with very low regenerative capacity and high metabolic activity, is vulnerable to chronic, although low-grade, MA. To syst...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/13/4/549 |
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| author | Yamin Liu Amina Atiq Anna Peterson Mikayla Moody Ashkan Novin Alix C. Deymier Junaid Afzal Kshitiz |
| author_facet | Yamin Liu Amina Atiq Anna Peterson Mikayla Moody Ashkan Novin Alix C. Deymier Junaid Afzal Kshitiz |
| author_sort | Yamin Liu |
| collection | DOAJ |
| description | Metabolic acidosis (MA) is a highly prevalent disorder in a significant proportion of the population, resulting from imbalance in blood pH homeostasis. The heart, being an organ with very low regenerative capacity and high metabolic activity, is vulnerable to chronic, although low-grade, MA. To systematically characterize the effect of low-grade MA on the heart, we treated male and female mice with NH<sub>4</sub>Cl supplementation for 2 weeks and analyzed their blood chemistry and transcriptomic signature of the heart tissue. The reduction of pH and plasma bicarbonate levels without an associated change in anion gap indicated a physiological manifestation of low-grade MA with minimal respiratory compensation. On transcriptomic analysis, we observed changes in cardiac-specific genes with significant gender-based differences due to MA. We found many genes contributing to dilated cardiomyopathy to be altered in males, more than in females, while cardiac contractility and Na/K/ATPase-Src signaling were affected in the opposite way. Our model presents a systems-level understanding of how the cardiovascular tissue is affected by MA. As low-grade MA is a common ailment with many dietary and pharmaceutical interventions, our work presents avenues to limit chronic cardiac damage and disease manifestation, as well as highlighting the sex differences in MA-induced cardiovascular damage. |
| first_indexed | 2024-03-11T04:45:55Z |
| format | Article |
| id | doaj.art-af8d4479930b4eb2b898dd04c2a5b4d5 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-11T04:45:55Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-af8d4479930b4eb2b898dd04c2a5b4d52023-11-17T20:25:03ZengMDPI AGMetabolites2218-19892023-04-0113454910.3390/metabo13040549Metabolic Acidosis Results in Sexually Dimorphic Response in the Heart TissueYamin Liu0Amina Atiq1Anna Peterson2Mikayla Moody3Ashkan Novin4Alix C. Deymier5Junaid Afzal6Kshitiz7Department of Biomedical Engineering, University of Connecticut Health, Farmington, CT 06032, USADepartment of Biomedical Engineering, University of Connecticut Health, Farmington, CT 06032, USADepartment of Biomedical Engineering, University of Connecticut Health, Farmington, CT 06032, USADepartment of Biomedical Engineering, University of Connecticut Health, Farmington, CT 06032, USADepartment of Biomedical Engineering, University of Connecticut Health, Farmington, CT 06032, USADepartment of Biomedical Engineering, University of Connecticut Health, Farmington, CT 06032, USADivision of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, CA 94158, USADepartment of Biomedical Engineering, University of Connecticut Health, Farmington, CT 06032, USAMetabolic acidosis (MA) is a highly prevalent disorder in a significant proportion of the population, resulting from imbalance in blood pH homeostasis. The heart, being an organ with very low regenerative capacity and high metabolic activity, is vulnerable to chronic, although low-grade, MA. To systematically characterize the effect of low-grade MA on the heart, we treated male and female mice with NH<sub>4</sub>Cl supplementation for 2 weeks and analyzed their blood chemistry and transcriptomic signature of the heart tissue. The reduction of pH and plasma bicarbonate levels without an associated change in anion gap indicated a physiological manifestation of low-grade MA with minimal respiratory compensation. On transcriptomic analysis, we observed changes in cardiac-specific genes with significant gender-based differences due to MA. We found many genes contributing to dilated cardiomyopathy to be altered in males, more than in females, while cardiac contractility and Na/K/ATPase-Src signaling were affected in the opposite way. Our model presents a systems-level understanding of how the cardiovascular tissue is affected by MA. As low-grade MA is a common ailment with many dietary and pharmaceutical interventions, our work presents avenues to limit chronic cardiac damage and disease manifestation, as well as highlighting the sex differences in MA-induced cardiovascular damage.https://www.mdpi.com/2218-1989/13/4/549metabolic acidosisdilated cardiomyopathycardiac contractilitychronic cardiac damagesexual dimorphismacidosis |
| spellingShingle | Yamin Liu Amina Atiq Anna Peterson Mikayla Moody Ashkan Novin Alix C. Deymier Junaid Afzal Kshitiz Metabolic Acidosis Results in Sexually Dimorphic Response in the Heart Tissue Metabolites metabolic acidosis dilated cardiomyopathy cardiac contractility chronic cardiac damage sexual dimorphism acidosis |
| title | Metabolic Acidosis Results in Sexually Dimorphic Response in the Heart Tissue |
| title_full | Metabolic Acidosis Results in Sexually Dimorphic Response in the Heart Tissue |
| title_fullStr | Metabolic Acidosis Results in Sexually Dimorphic Response in the Heart Tissue |
| title_full_unstemmed | Metabolic Acidosis Results in Sexually Dimorphic Response in the Heart Tissue |
| title_short | Metabolic Acidosis Results in Sexually Dimorphic Response in the Heart Tissue |
| title_sort | metabolic acidosis results in sexually dimorphic response in the heart tissue |
| topic | metabolic acidosis dilated cardiomyopathy cardiac contractility chronic cardiac damage sexual dimorphism acidosis |
| url | https://www.mdpi.com/2218-1989/13/4/549 |
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