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Review
. 2022 Mar 9:13:841692.
doi: 10.3389/fimmu.2022.841692. eCollection 2022.

Angiotensin-(1-7) as a Potential Therapeutic Strategy for Delayed Cerebral Ischemia in Subarachnoid Hemorrhage

Filippo Annoni  1   2 , Federico Moro  1 , Enrico Caruso  1   3 , Tommaso Zoerle  3   4 , Fabio Silvio Taccone  2 , Elisa R Zanier  1
Affiliations
Review

Angiotensin-(1-7) as a Potential Therapeutic Strategy for Delayed Cerebral Ischemia in Subarachnoid Hemorrhage

Filippo Annoni et al. Front Immunol. .

Abstract

Aneurysmal subarachnoid hemorrhage (SAH) is a substantial cause of mortality and morbidity worldwide. Moreover, survivors after the initial bleeding are often subject to secondary brain injuries and delayed cerebral ischemia, further increasing the risk of a poor outcome. In recent years, the renin-angiotensin system (RAS) has been proposed as a target pathway for therapeutic interventions after brain injury. The RAS is a complex system of biochemical reactions critical for several systemic functions, namely, inflammation, vascular tone, endothelial activation, water balance, fibrosis, and apoptosis. The RAS system is classically divided into a pro-inflammatory axis, mediated by angiotensin (Ang)-II and its specific receptor AT1R, and a counterbalancing system, presented in humans as Ang-(1-7) and its receptor, MasR. Experimental data suggest that upregulation of the Ang-(1-7)/MasR axis might be neuroprotective in numerous pathological conditions, namely, ischemic stroke, cognitive disorders, Parkinson's disease, and depression. In the presence of SAH, Ang-(1-7)/MasR neuroprotective and modulating properties could help reduce brain damage by acting on neuroinflammation, and through direct vascular and anti-thrombotic effects. Here we review the role of RAS in brain ischemia, with specific focus on SAH and the therapeutic potential of Ang-(1-7).

Keywords: acute brain injury; anoxic injury; delayed cerebral ischemia (DCI); renin–angiotensin system (RAS); subarachnoid hemorrhage (SAH).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the renin–angiotensin system (RAS). Black boxes are for the effectors, red ones for enzymes, purple ones for pharmacological inhibitors, green ones for pharmacological stimulators, and gold boxes for receptors.
Figure 2
Figure 2
RAS modulation through AT1R, AT2R, MasR counteract neuroinflammation across several brain pathological brain conditions. PD, Parkinson’s disease; AD, Alzheimer’s disease; TBI, traumatic brain injury; ACE, angiotensin-converting enzyme; Ang, angiotensin; ROS, reactive oxygen species. Image created with BioRender.com.
Figure 3
Figure 3
Schematic representation of the positive effects of Ang-(1–7) after subarachnoid hemorrhage (SAH). Image created with BioRender.com.
See this image and copyright information in PMC

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