Local Renin-Angiotensin II Systems, Angiotensin-Converting Enzyme and its Homologue ACE2: Their Potential Role in the Pathogenesis of Chronic Obstructive Pulmonary Diseases, Pulmonary Hypertension and Acute Respiratory Distress Syndrome

Abstract

Renin-angiotensin II-aldosterone axis has long been known as a regulator of blood pressure and fluid homeostasis. Yet, local renin-angiotensin II systems have been discovered and novel actions of angiotensin II (AngII) have emerged among which its ability to act as a immunomodulator and profibrotic molecule. The enzyme responsible for its synthesis, Angiotensin-converting-enzyme (ACE), is present in high concentrations in lung tissue. In the present paper, we review data from studies of the past decade that implicate AngII and functional polymorphisms of the ACE gene that increase ACE activity with increased susceptibility for asthma and chronic obstructive pulmonary disease (COPD) and for pulmonary hypertension. Moreover, drugs that inhibit the synthesis of AngII (ACE inhibitors) or that antagonize its actions on its receptors (Angiotensin II receptor blockers -ARBs) have been shown to provide beneficial effects. Another recent discovery reviewed is the presence of a homologue of ACE, ACE2, which cleaves a single amino acid from AngII and forms a heptapeptide with vasodilatory actions, Ang 1-7. The balance between ACE and ACE2 is crucial for controlling AngII levels. ACE and ACE2 also appear to modify the severity of Acute Respiratory Distress Syndrome (ARDS), with ACE2 playing a protective role. Finally, mention is made to the recent discovery of ACE2 as a receptor for the SARS Corona Virus.

Endothelin-1 Downregulates Angiotensin-Converting Enzyme-2 Expression in Human Bronchial Epithelial Cells

“…Thus, in addition to its reported pro-inflammatory effects, ET-1 may also promote COPD pathogenesis and progression by inhibiting ACE2 expression and activity, which leads to: (1) increased concentration of Ang II, a recognized mediator of airway inflammation associated with COPD and other lung diseases [4,21,23]; (2) decreased concentration of Ang 1-7 , a putatively protective peptide for the lung mainly by antagonizing the effects of Ang II. In other words, ET-1 may enhance the pathophysiological effects of the RAS in COPD pathogenesis and progression by downregulating ACE2 expression.…”

“…The renin-angiotensin system (RAS) is implicated in the pathogenesis of COPD through its involvement in inducing pro-inflammatory mediators in the lung [3]. In the RAS, angiotensin-converting enzyme (ACE) metabolizes angiotensin I (Ang I) to form angiotensin II (Ang II), which stimulates the release of cytokines and has an immunomodulatory effect on T-cell responses that mediate the lung tissue injury associated with COPD [4]. The RAS can also generate reactive oxygen species via the Ang II type I receptor (AT1R), promoting mitochondrial dysfunction [5], which contributes to the oxidative stress and impaired redox signalling observed in COPD [6].…”

Медикаментозне Управління Окислювально-Відновним Станом Організму При Захворюваннях Органів Дихання (Частина 1)

“…Активность локальной интрапульмональной ренинангиотензи-новой системы высоко коррелирует со скоростью развития фиброза легкого [4], риском развития БА, ХОБЛ и легочной гипертензии [2,32]. Ингибиторы ангиотензинпревращающего фермента (АПФ) не только уменьшают уровень образования ангиотен-зина II, но и непосредственно подавляют экспрес-сию субъединиц p22phox НАДФH-оксидазы [8,49].…”

Renin^|^ndash;Angiotensin System, Hypertension, and Chronic Kidney Disease: Pharmacogenetic Implications

“…Recently, several local RASs have been discovered in organs such as the heart, brain, pancreas, kidney, and adipose tissue, and novel actions of angiotensin II have emerged among which is its ability to act as immunomodulator, profibrotic molecule, and inhibitor of insulin signaling (43,44). However, the exact role and influence of the local RAS on specific organ diseases or studied phenotypes is not completely understood (45).…”