Mitochondrial Monoamine Oxidase: Another Player in Pulmonary Hypertension?

Sommer, Natascha; Schulz, Rainer

doi:10.1165/rcmb.2020-0523ed

Cited by 5 publications

(5 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MAOs have also been proposed to play an important role in pulmonary hypertension [ 168 ]. In rats, pulmonary hypertension secondary to monocrotaline injection [ 139 ], sugen5416/hypoxia, or pulmonary artery banding [ 140 ] upregulates MAO-A expression in the pulmonary vasculature and the failing right ventricle.…”

Section: Monoamine Oxidases (Mao)mentioning

confidence: 99%

Importance of Mitochondria in Cardiac Pathologies: Focus on Uncoupling Proteins and Monoamine Oxidases

Schulz

Schlüter

2023

IJMS

Self Cite

View full text Add to dashboard Cite

On the one hand, reactive oxygen species (ROS) are involved in the onset and progression of a wide array of diseases. On the other hand, these are a part of signaling pathways related to cell metabolism, growth and survival. While ROS are produced at various cellular sites, in cardiomyocytes the largest amount of ROS is generated by mitochondria. Apart from the electron transport chain and various other proteins, uncoupling protein (UCP) and monoamine oxidases (MAO) have been proposed to modify mitochondrial ROS formation. Here, we review the recent information on UCP and MAO in cardiac injuries induced by ischemia-reperfusion (I/R) as well as protection from I/R and heart failure secondary to I/R injury or pressure overload. The current data in the literature suggest that I/R will preferentially upregulate UCP2 in cardiac tissue but not UCP3. Studies addressing the consequences of such induction are currently inconclusive because the precise function of UCP2 in cardiac tissue is not well understood, and tissue- and species-specific aspects complicate the situation. In general, UCP2 may reduce oxidative stress by mild uncoupling and both UCP2 and UCP3 affect substrate utilization in cardiac tissue, thereby modifying post-ischemic remodeling. MAOs are important for the physiological regulation of substrate concentrations. Upon increased expression and or activity of MAOs, however, the increased production of ROS and reactive aldehydes contribute to cardiac alterations such as hypertrophy, inflammation, irreversible cardiomyocyte injury, and failure.

show abstract

Section: Monoamine Oxidases (Mao)mentioning

confidence: 99%

Importance of Mitochondria in Cardiac Pathologies: Focus on Uncoupling Proteins and Monoamine Oxidases

Schulz

Schlüter

2023

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…HIF-1α affects NO metabolism, contributing to PAH severity. Understanding the HIF-1α pathway provides insights into potential therapeutic targets in PAH [18,19].…”

Section: Molecular Mechanisms In Pahmentioning

confidence: 99%

“…It also restores intracellular phosphocreatine resources, optimizing cell metabolism and offering cytoprotective effects. Additionally, mitochondrial fission inhibition via mitochondrial division inhibitor 1 (Mdivi-1) reduces PASMC proliferation and restores ATP synthesis [15,17,19].…”

Section: Therapeutic Approaches In Pulmonary Hypertensionmentioning

confidence: 99%

Pulmonary Hypertension: Unveiling Molecular Mechanisms, Diagnosis, and Therapeutic Targets

Gredic,

Hadzic

2023

JPM

View full text Add to dashboard Cite

show abstract

“…While the importance of MAOs in the pathophysiology of left ventricular diseases is well-established [ 19 , 20 , 21 , 22 ], data on their importance for RV diseases are rare, but involvement in PH has been proposed [ 23 ]. In rats, PH secondary to monocrotaline injection [ 24 ], sugen5416/hypoxia, or pulmonary artery banding [ 25 ] upregulates MAO-A expression in the pulmonary vasculature and the failing RV.…”

Section: Introductionmentioning

confidence: 99%

Does Cell-Type-Specific Silencing of Monoamine Oxidase B Interfere with the Development of Right Ventricle (RV) Hypertrophy or Right Ventricle Failure in Pulmonary Hypertension?

Brosinsky,

Heger,

Sydykov

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

Increased mitochondrial reactive oxygen species (ROS) formation is important for the development of right ventricular (RV) hypertrophy (RVH) and failure (RVF) during pulmonary hypertension (PH). ROS molecules are produced in different compartments within the cell, with mitochondria known to produce the strongest ROS signal. Among ROS-forming mitochondrial proteins, outer-mitochondrial-membrane-located monoamine oxidases (MAOs, type A or B) are capable of degrading neurotransmitters, thereby producing large amounts of ROS. In mice, MAO-B is the dominant isoform, which is present in almost all cell types within the heart. We analyzed the effect of an inducible cardiomyocyte-specific knockout of MAO-B (cmMAO-B KO) for the development of RVH and RVF in mice. Right ventricular hypertrophy was induced by pulmonary artery banding (PAB). RV dimensions and function were measured through echocardiography. ROS production (dihydroethidium staining), protein kinase activity (PamStation device), and systemic hemodynamics (in vivo catheterization) were assessed. A significant decrease in ROS formation was measured in cmMAO-B KO mice during PAB compared to Cre-negative littermates, which was associated with reduced activity of protein kinases involved in hypertrophic growth. In contrast to littermates in which the RV was dilated and hypertrophied following PAB, RV dimensions were unaffected in response to PAB in cmMAO-B KO mice, and no decline in RV systolic function otherwise seen in littermates during PAB was measured in cmMAO-B KO mice. In conclusion, cmMAO-B KO mice are protected against RV dilatation, hypertrophy, and dysfunction following RV pressure overload compared to littermates. These results support the hypothesis that cmMAO-B is a key player in causing RV hypertrophy and failure during PH.

show abstract

Mitochondrial Monoamine Oxidase: Another Player in Pulmonary Hypertension?

Cited by 5 publications

References 15 publications

Importance of Mitochondria in Cardiac Pathologies: Focus on Uncoupling Proteins and Monoamine Oxidases

Importance of Mitochondria in Cardiac Pathologies: Focus on Uncoupling Proteins and Monoamine Oxidases

Pulmonary Hypertension: Unveiling Molecular Mechanisms, Diagnosis, and Therapeutic Targets

Does Cell-Type-Specific Silencing of Monoamine Oxidase B Interfere with the Development of Right Ventricle (RV) Hypertrophy or Right Ventricle Failure in Pulmonary Hypertension?

Contact Info

Product

Resources

About