Understanding the Pathogenesis of Cardiac Complications in Patients with Propionic Acidemia and Exploring Therapeutic Alternatives for Those Who Are Not Eligible or Are Waiting for Liver Transplantation
Abstract
:1. Introduction
2. Aim of the Review
- −
- The current knowledge of the pathogenetic mechanisms responsible for cardiac complications in PA;
- −
- The therapeutic options for the prevention or treatment of cardiac complications in PA.
3. Material and Methods
4. Results
4.1. Impaired Substrate Delivery to TCA Cycle and TCA Dysfunction
4.2. Secondary Mitochondrial Electron Transport (mtETC) Chain Dysfunction and Oxidative Stress
4.3. Coenzyme Q10 Deficiency
4.4. Metabolic Reprogramming
4.5. Carnitine Deficiency
4.6. Cardiac Excitation-Contraction Coupling Alteration
4.7. Genetics
4.8. Epigenetics
4.9. MicroRNAs
4.10. Micronutrients Deficiencies
4.10.1. Selenium
4.10.2. Iron
4.10.3. Vitamin D
4.10.4. Zinc
4.10.5. Thiamine
4.10.6. Riboflavin
4.10.7. Biotin
4.11. The Renin–Angiotensin–Aldosterone System
4.12. Increased Sympathetic Activation
5. Discussion
6. Conclusions and Future Directions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ACE | angiotensin-converting enzyme |
ACEi | ACE inhibitors |
aLQTS | acquired long QT syndrome |
ARBs | angiotensin II receptor blockers |
BB | beta-blockers |
BNP | brain natriuretic peptide |
CM | cardiomyopathy |
CoQ10 | Coenzyme Q10 |
CV | cardiovascular |
D,L-BHB | D,L-beta-hydroxybutyrate |
DCM | dilated cardiomyopathy |
FS | fractional shortening |
HAT | histone acetyltransferases |
HDACs | histone deacetylase |
HF | heart failure |
HFrEF | HF with reduced LVEF |
ID | iron deficiency |
Iv | intravenous |
iPSCs | induced pluripotent stem cells |
LT | liver transplantation |
LV | left ventricular |
LVEF | left ventricular ejection fraction |
miRNAs | microRNAs |
MRA | mineralcorticoid receptor antagonists |
mtETC | mitochondrial electron transport chain |
NT-ProBNP | amino-terminal fragment of the BNP |
OXPHOS | oxidative phosphorylation |
PA | propionic acidemia |
PCC | propionyl-CoA carboxylase |
RAAS | renin–angiotensin–aldosterone system |
ROS | reactive oxygen species |
SCA | sudden cardiac arrest |
SGLT2 | Na+-glucose cotransporter-2 |
TCA | tricarboxylic acid |
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Accepted | Potential Harmful | References | |
---|---|---|---|
ACE-inhibitors (ACE-i) | X | [7] | |
Mineralcorticoid receptor antagonists (MRA) | X | - | |
Angiotensin receptor-neprilysin inhibitor sacubitril/valsartan | X | - | |
Na+-glucose cotransporter-2 (SGLT2) inhibitors | X | [99,100] | |
Beta-blockers (BBs) | X | [7,102] |
Heart Failure in General | References | Propionic Acidemia | References | |
---|---|---|---|---|
Coenzyme Q10 | Not conclusive results. | [15,43] | Weak evidence | [25,29] |
Vitamin D | Lack of evidence. Vitamin D deficiency has been described in some cases of reversible HF associated with severe hypocalcemia, but routine supplementation has not proven beneficial. | [15,83] | No data | - |
Thiamine | Lack of evidence. Thiamine deficiency is recognized as a cause of HF, but routine supplementation has not proven beneficial. | [14,15] | No data | - |
Carnitine | Lack of evidence | [15] | Carnitine supplementation is recommended to maintain its plasmatic level within the normal range, thus improving the metabolic stability of patients | [4] |
Vitamin E | Potentially harmful. | [15] | No data | - |
Selenium | Selenium deficiency is recognized as a cause of HF. A common consensus is building on the idea that only patients with selenium deficiency could benefit from selenium supplements. | [14,43,75] | No data | - |
Iron | Iron deficiency has been associated with clinical instability. Treatment is recommended in the case of iron depletion. Routine oral supplementation has not proven beneficial. | [14,15] | No data | - |
Zinc | Routine supplementation has not proven beneficial. Little evidence supports zinc supplementation in the case of zinc deficiency. | [15,86,88] | No data | - |
Riboflavin | Multivitamins have not proven beneficial. | [15] | No data | - |
Biotin | Multivitamins have not proven beneficial. | [15] | Its use in the chronic management of PA patients lacks evidence of efficacy | [57] |
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Maines, E.; Moretti, M.; Vitturi, N.; Gugelmo, G.; Fasan, I.; Lenzini, L.; Piccoli, G.; Gragnaniello, V.; Maiorana, A.; Soffiati, M.; et al. Understanding the Pathogenesis of Cardiac Complications in Patients with Propionic Acidemia and Exploring Therapeutic Alternatives for Those Who Are Not Eligible or Are Waiting for Liver Transplantation. Metabolites 2023, 13, 563. https://doi.org/10.3390/metabo13040563
Maines E, Moretti M, Vitturi N, Gugelmo G, Fasan I, Lenzini L, Piccoli G, Gragnaniello V, Maiorana A, Soffiati M, et al. Understanding the Pathogenesis of Cardiac Complications in Patients with Propionic Acidemia and Exploring Therapeutic Alternatives for Those Who Are Not Eligible or Are Waiting for Liver Transplantation. Metabolites. 2023; 13(4):563. https://doi.org/10.3390/metabo13040563
Chicago/Turabian StyleMaines, Evelina, Michele Moretti, Nicola Vitturi, Giorgia Gugelmo, Ilaria Fasan, Livia Lenzini, Giovanni Piccoli, Vincenza Gragnaniello, Arianna Maiorana, Massimo Soffiati, and et al. 2023. "Understanding the Pathogenesis of Cardiac Complications in Patients with Propionic Acidemia and Exploring Therapeutic Alternatives for Those Who Are Not Eligible or Are Waiting for Liver Transplantation" Metabolites 13, no. 4: 563. https://doi.org/10.3390/metabo13040563