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Left Ventricular Hypertrophy: Roles of Mitochondria CYP1B1 and Melatonergic Pathways in Co-Ordinating Wider Pathophysiology

1
CRC Scotland & London, London E14 6JE, UK
2
Division of Internal Medicine and Chronobiology Unit, Department of Medical Sciences, Fondazione IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, 71013 Foggia, Italy
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(16), 4068; https://doi.org/10.3390/ijms20164068
Received: 23 July 2019 / Revised: 11 August 2019 / Accepted: 16 August 2019 / Published: 20 August 2019
(This article belongs to the Special Issue Novel Strategies for Cardiac Protection and Regeneration)
Left ventricular hypertrophy (LVH) can be adaptive, as arising from exercise, or pathological, most commonly when driven by hypertension. The pathophysiology of LVH is consistently associated with an increase in cytochrome P450 (CYP)1B1 and mitogen-activated protein kinases (MAPKs) and a decrease in sirtuins and mitochondria functioning. Treatment is usually targeted to hypertension management, although it is widely accepted that treatment outcomes could be improved with cardiomyocyte hypertrophy targeted interventions. The current article reviews the wide, but disparate, bodies of data pertaining to LVH pathoetiology and pathophysiology, proposing a significant role for variations in the N-acetylserotonin (NAS)/melatonin ratio within mitochondria in driving the biological underpinnings of LVH. Heightened levels of mitochondria CYP1B1 drive the ‘backward’ conversion of melatonin to NAS, resulting in a loss of the co-operative interactions of melatonin and sirtuin-3 within mitochondria. NAS activates the brain-derived neurotrophic factor receptor, TrkB, leading to raised trophic signalling via cyclic adenosine 3′,5′-monophosphate (cAMP)-response element binding protein (CREB) and the MAPKs, which are significantly increased in LVH. The gut microbiome may be intimately linked to how stress and depression associate with LVH and hypertension, with gut microbiome derived butyrate, and other histone deacetylase inhibitors, significant modulators of the melatonergic pathways and LVH more generally. This provides a model of LVH that has significant treatment and research implications. View Full-Text
Keywords: left ventricular hypertrophy; mitochondria; CYP1B1; melatonin; N-aceytlserotonin; MAPK; sirtuin; gut microbiome; treatment; aryl hydrocarbon receptor left ventricular hypertrophy; mitochondria; CYP1B1; melatonin; N-aceytlserotonin; MAPK; sirtuin; gut microbiome; treatment; aryl hydrocarbon receptor
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Anderson, G.; Mazzoccoli, G. Left Ventricular Hypertrophy: Roles of Mitochondria CYP1B1 and Melatonergic Pathways in Co-Ordinating Wider Pathophysiology. Int. J. Mol. Sci. 2019, 20, 4068.

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