The role of Immunity in Fabry Disease and Hypertension: A Review of a Novel Common Pathway

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.

Access to dental care and blood pressure profiles in adults with high socioeconomic status

“…40,41 Toll-like receptor 4 and activated perivascular T cells were shown to trigger vascular inflammation in response to hypertensive stimuli, ultimately leading to arterial remodeling and impaired vasoreactivity. 40,42 There is evidence of a hypertensionspecific immune host response to periodontal bacteria, 43 and that the oral-gut microbiota is involved in BP regulation. 44 Importantly, periodontal treatment and a healthy oral microbiota significantly modulate adaptive immunity.…”

“…Hypertension itself is considered a condition associated with low‐grade inflammation involving both innate and adaptive immunity 40,41 . Toll‐like receptor 4 and activated perivascular T cells were shown to trigger vascular inflammation in response to hypertensive stimuli, ultimately leading to arterial remodeling and impaired vasoreactivity 40,42 . There is evidence of a hypertension‐specific immune host response to periodontal bacteria, 43 and that the oral‐gut microbiota is involved in BP regulation 44 .…”

Prevalence of hypertension and associated risks in hospitalized patients with COVID-19: a meta-analysis of meta-analyses with 1468 studies and 1,281,510 patients

“…Based on the results of published studies and reports, a significant number of high-risk individuals and groups, whose mortality risk and severe complications are higher than others, have been identified since the onset of the COVID-19 pandemic [10][11][12][13][14][15][16]. Patients with hypertension belong to one of these high-risk groups [17][18][19].…”

“…Additionally, some researchers started conducting systematic reviews and meta-analyses using the findings of the studies [18,19,26,27]. Although these studies have presented comprehensive and helpful information, it seems that study results differ from one another.…”

X Chromosome Inactivation in Carriers of Fabry Disease: Review and Meta-Analysis

“…The inflammatory response can also be triggered by the vascular alteration. In fact, vascular remodeling could reduce the arterial compliance, determining upregulation of the renin-angiotensin system and the increase of angiotensin 1 and 2 in endothelial cells [ 31 , 32 ], which trigger the inflammation [ 31 , 33 ]. The consequence of inflammation is the release of pro-thrombotic factors in the vessels, increasing the risk of ischemia by increasing the extracellular matrix deposition and fibrosis [ 31 , 34 ].…”