Anne Järve, Max Delbrück Center for Molecular Medicine, Berlin, Germany

Reduction of organ damage in SCI using the renin-angiotensin system (RAS)

Funded in: 2014, 2015, 2016


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Problem: Cardiovascular dysfunction is one of the leading causes of morbidity and mortality in both acute and chronic stages of SCI.

Target: The protective arm of the endocrine system regulating the blood pressure (renin-angiotensin system, angiotensin-(1-7), Mas and AT2 receptors)

Goal: Finding a novel treatment approach for SCI with protective effects on neurons in the spinal cord and on cardiovascular organs.

 

Spinal cord injury (SCI) leads to expansion of the initial damage by ischemia, oxidative stress and inflammation, resulting in devastating disability, uncontrolled blood pressure changes and vulnerability of multiple organ systems including heart. This cardiovascular dysfunction is one of the leading causes of morbidity and mortality in both acute and chronic stages of SCI. The renin-angiotensin system (RAS) is a potent regulator of blood pressure and its classical harmful components (angiotensin II and the AT1 receptor) become activated after SCI, initiating the target organ damage.
However, there are also protective arms to RAS (comprising angiotensin-(1-7), Mas and AT2 receptors) counteracting the detrimental effects of the classical RAS, stimulation of which has been proven to be efficient in many cardiovascular disease states.
Intriguingly, stimulation of one of the protective RAS components (AT2 receptors) has been shown to directly promote the axon outgrowth, as well as the optic nerve and SCI recovery through activation of neurotrophic, anti-inflammatory, and anti-oxidant pathways.

This excellent feature of the protective RAS to act locally and systemically inspires to

  • explore the neuroprotective potential of protective RAS in SCI by the pharmacological and genetic modulation/ablation of its components (angiotensin-(1-7),Mas, and AT1 receptors)
  • evaluate the systemic protective effects in cardiovascular organs

This study will introduce a novel approach for the treatment of SCI with simultaneous protective effects on the spinal cord and the cardiovascular target organs.