The Role of the ACE2/MasR Axis in Ischemic Stroke: New Insights for Therapy

Figures

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  Figure 1. Classification of stroke subtypes. Stroke is classified into two major forms—ischemic (85%) and hemorrhagic (15%) groups.

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  Figure 2. Classical and alternative pathways of the renin angiotensin system (RAS). In the classical axis of RAS, angiotensin-converting enzyme (ACE) converts angiotensin I (Ang I) into angiotensin II (Ang II). Ang II activates angiotensin type 1 receptor (AT1R) to trigger vasoconstriction, inflammation, fibrosis, and cellular hypertrophy, and apoptosis. In the alternative axis, ACE2 converts Ang II into Ang (1–7) or Ang I into Ang (1–9). Ang (1–9) is converted to Ang (1–7) by the enzymatic activity of ACE or neprilysin. Ang (1–7) binds to either AT2R or MasR to exert vasodilator, anti-inflammatory, and anti-apoptotic effects.

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  Figure 3. Pathophysiological mechanisms involved in ischemic stroke. The reduction in blood flow, nutrient supply, and energy as a result of cerebral artery occlusion leads to many complex pathophysiological events including energy failure, glutamate excitotoxicity, elevation of intracellular Ca2+ levels, peri-infarct depolarization (spreading depression), impairment of mitochondria function, generation of reactive oxygen species (ROS), activation of microglia, secretion of pro-inflammatory cytokines/chemokines, inflammatory responses, and cell death.