ACE in COPD: a therapeutic target?
- 1Portex Anaesthesia, Intensive Therapy and Respiratory Unit, Institute of Child Health, London WC1N 1EH, UK
- 2Cardiovascular Genetics, Rayne Institute, London WC1E 6JJ, UK
- Correspondence to:
Dr H Montgomery, Cardiovascular Genetics, 3rd Floor, Rayne Institute, 5 University Street, London WC1E 6JJ, UK;
h.montgomery{at}ucl.ac.uk
Chronic lowering of ACE activity may have profound benefits in the long term treatment of patients with chronic lung disease such as COPD.
As a component of the circulating (or endocrine) renin-angiotensin system (RAS), angiotensin converting enzyme (ACE) plays an important role in circulatory homeostasis. ACE cleaves angiotensin I to yield the potent vasopressor octapeptide angiotensin II while simultaneously cleaving vasodilator kinins, and angiotensin II drives renal salt/water retention through release of adrenal aldosterone. In this way, ACE exerts tonic influence on water balance and blood pressure. However, local cellular (autocrine) and organ (paracrine) RAS exist in tissues as diverse as human heart,1 skeletal muscle,2 fat,3 and brain,4 where they play a variety of roles. Whether in the circulation or the tissues,1,5 the presence (insertion, I allele) rather than the absence (deletion, D allele) of a 287 base pair fragment in the human ACE gene is associated with increased ACE activity.
Increasing RAS activity certainly exerts powerful proinflammatory effects in many systems,6–10 while angiotensin II has direct profibrotic actions.11 Local RAS has …
