The role of Immunity in Fabry Disease and Hypertension: A Review of a Novel Common Pathway
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REVIEW ARTICLE
The role of Immunity in Fabry Disease and Hypertension: A Review of a Novel Common Pathway Rita Del Pinto1 · Claudio Ferri1 Received: 14 August 2020 / Accepted: 28 September 2020 © The Author(s) 2020
Abstract Fabry disease is a progressive, X-linked inherited lysosomal storage disorder where accumulation of glycosphingolipids increases the risk for early cardiovascular complications, including heart failure, stroke, and end stage renal disease. Besides disease-specific therapy, blood pressure (BP) control is of central importance in Fabry disease to reduce disease progression and improve prognosis. Both Fabry disease and hypertension are characterized by the activation of the innate component of the immune system, with Toll-like receptor 4 (TLR4) as a common trigger to the inflammatory cascade. The renin-angiotensin system (RAS) participates in the establishment of low-grade chronic inflammation and redox unbalance that contribute to organ damage in the long term. Besides exploiting the anti-inflammatory effects of RAS blockade and enzyme replacement therapy, targeted therapies acting on the immune system represent an appealing field of research in these conditions. The aim of this narrative review is to examine the issue of hypertension in the setting of Fabry disease, focusing on the possible determinants of their reciprocal relationship, as well as on the related clinical and therapeutic implications. Keywords Hypertension · Fabry disease · Inflammation · Immune system · Renin-angiotensin system · Oxidative stress
1 Introduction Fabry disease is a progressive, X-linked inherited lysosomal storage disorder affecting the glycosphingolipid metabolism [1]. The underlying defect, resulting from mutations in the GLA gene, concerns the activity of the lysosomal enzyme alpha-galactosidase A, whose reduced or absent activity leads to the progressive accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3), in the affected cells and in body fluids [2]. Cellular dysfunction and microvascular pathology that occur early in the disease history trigger a cascade of events involving impaired metabolism, immune system activation, and defective tissue perfusion that eventually induce the development of irreversible fibrosis at crucial sites (i.e. heart, kidney) [1]. Although the classical phenotype is more
* Rita Del Pinto [email protected] 1
Division of Internal Medicine and Nephrology, Department of Life, Health and Environmental Sciences, San Salvatore Hospital, University of L’Aquila, San Salvatore Hospital, Building Delta 6, L’Aquila, Italy
typical of males, it may also occur among females due to random X-inactivation [1]. Fabry disease is underdiagnosed. In the late Nineties, its estimated prevalence ranged between 1:117,000 [3] and 1:476,000 [4], but more recent evidence claims it to be reconsidered at between 1:3100 [5] and 1:8500 [6, 7], or even lower (1:1818 according to a screening campaign in South Sardinia [8]). The exclusion of pos
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