About this Research Topic

Background

Essentially all biological processes are exquisitely sensitive to acid-base chemistry due to the propensity for proteins to undergo pH-dependent structural, and hence functional, post-translational modifications. These modulatory actions can emerge as an outcome of metabolic pathways that handle weak acids or weak bases and result in a net shift in pH. The heartbeat, for example, requires considerable metabolite turnover, which inadvertently loads the tissue with acids such as CO2, but also chemicals including lactic acid under inadequate oxygen or as a result of acquired or inherited disease-related metabolic remodelling. A failure of blood perfusion to adequately wash-away the excess of acid or base would accentuate these pH disturbances.

Changes in intra- or extracellular pH can occur in a physiological or pathological context, where they may underpin a signalling modality or be part of a disease process, respectively. This is particularly relevant to the cardiovascular system, where it is well documented that pH can affect cardiac contractility, rhythm, and growth, as well as in vasculature where it affects local blood flows. For example, acid-evoked vasodilation in metabolically-active vascular beds serves a physiological purpose to match blood flow to local demand. Given the powerful actions of pH, virtually all cells are equipped with a dedicated homeostatic apparatus to regulate intracellular pH, ultimately by means of membrane-bound transporters that handle H+ ions or their chemical equivalents. However, their over-drive in cardiac myocytes can produce knock-on effects on physiology, such as aberrant growth or arrhythmia. Indeed, a common chemical signature of many disorders affecting the cardiovascular system is acidosis. To understand pH-related disease processes, a large volume of work has been undertaken to develop methods for imaging pH and investigating how acid-base disturbances affect biology, from molecular details of the titratable site to the organ-level phenotype.

The aim of this volume is to provide a comprehensive and balanced survey of acid-base disorders in the cardiovascular system. Through a series of primary research articles and reviews, this collection describes the mechanisms underpinning pH disturbances and how these can be measured. It then explores our understanding of how pH serves as a physiological cue for regulating cardiovascular physiology, and how this may become aberrant in diseases processes. Authors present the canonical view concerning the causal link between pH and diseases of the vasculature and the heart.

Keywords: pH sensing, pH regulation, metabolism, acidosis, myocardium, vasculature, disease

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