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Environmental stress and hypertension: the disregarded role of HSP70

Journal of Human Hypertension (2024)Cite this article

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Recent comprehensive reviews have updated the role of environmental stress in the global incidence in hypertension [1,2,3]. However, the participation of the heat shock protein response generated by damaging environment in the prohypertensive inflammatory reactivity is unrecognized. The present contribution recapitulates the association of HSP70 overexpression with hypertension [4,5,6] and the evidence that stimulation of HSP70 is a critical consequence of injurious surroundings. Discussion will be focused in noise and air pollution because these are the recognized environmental risk factors that are specifically addressed in the most recent reviews [2, 3].

Heat shock proteins (HSPs) are a family of proteins reported initially to be induced by heat stress in the Drosophila melanogaster by Ferruccio Ritossa in 1962 [7] and subsequently shown to be constitutively present and to increase in response to any injurious stress, when they may represent as much as much as 15% of the total protein content of the cell. There are 9 major families of eukaryotic HSPs and 13 members of the HSP70 superfamily that is the most extensively studied. The primary function of HSPs is protective and the stress-induced HSP70 is an evolutionary preserved response with a chaperone-like function to safeguard proteostasis [8]. Nevertheless, HSP70 may also drive an inflammatory cytokine production, initially identified by its CD-14 dependent binding to the membrane of monocytes and generation of IL-6, hence the name “chaperokine” and its recognition as a danger-associated molecular pattern (DAMP) [9].

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Fig. 1: Systemic proinflammatory effects of HSP70.
Fig. 2: Specific epitopes of mycobacterial HSP70 [18, 19] injected in the foot pads induce delayed-type hypersensitivity, and if followed by intrarenal administration of HSP70, there is development of kidney tubulointerstitial inflammation and salt-sensitive hypertension.
Fig. 3: Environmental stress stimulation of HSP70 and hypertension.

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  1. Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Ciudad de México, Mexico

    Bernardo Rodriguez-Iturbe

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Rodriguez-Iturbe, B. Environmental stress and hypertension: the disregarded role of HSP70. J Hum Hypertens (2024). https://doi.org/10.1038/s41371-024-00917-2

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