Hepcidin: A missing link at the interface of malaria and hypertension

Abstract

Malaria and hypertension are seemingly unrelated communicable and non-communicable diseases, both highly pervasive in the global south. There is a debate about the potential connection between these two disorders beyond any obvious factors. The emerging evidence suggests an emerging genetic selection pressure for hypertension in malaria-endemic regions. Furthermore, the impact of the liver hormone hepcidin, which has been overlooked, is significant in the development of hypertension due to malaria. Malaria exposure leads to changes in iron metabolism through the regulation of hepcidin, resulting in iron deficiency and, consequently, the development of hypertension.

Keywords: Hepcidin; Hypertension; Malaria; Plasmodium.

Graphical abstract

Figure 1

Schematic representation illustrating the role of hepcidin in malaria-induced hypertension. Plasmodium infection triggers an inflammatory immune response in the host (1) that results in the release of hepcidin hormone from the liver (2). Hepcidin release (3) causes ferroportin degradation in enterocytes (4) and other cells (not shown here), thereby reducing the systemic iron pool (5), which leads to iron deficiency (6). Hepcidin-mediated iron deficiency directly affects pulmonary artery hypertension (7), ultimately causing hypertension (8) and heart failure. In addition, hepcidin is associated with systolic blood pressure (4a) and is a strong predictor of arterial stiffness (4b), exacerbating atherosclerosis (4c) and hypertension (4d), which are the precursor events to hypertension. The indirect hypothesis refers to genetic variations in human renin-angiotensin genes, which may provide protection against severe malaria. The dashed arrows represent sporadic observations and nonproven hypotheses. The figure was prepared using BioRender.