Abstract
There is mounting evidence that pulmonary arterial hypertension (PAH), asthma and chronic obstructive pulmonary disease (COPD) share important pathological features, including inflammation, smooth muscle contraction and remodeling. No existing drug provides the combined potential advantages of reducing vascular- and bronchial-constriction, and anti-inflammation. Vasoactive intestinal peptide (VIP) is widely expressed throughout the cardiopulmonary system and exerts a variety of biological actions, including potent vascular and airway dilatory actions, potent anti-inflammatory actions, improving blood circulation to the heart and lung, and modulation of airway secretions. VIP has emerged as a promising drug candidate for the treatment of cardiopulmonary disorders such as PAH, asthma, and COPD. Clinical application of VIP has been limited in the past for a number of reasons, including its short plasma half-life and difficulty in administration routes. The development of long-acting VIP analogues, in combination with appropriate drug delivery systems, may provide clinically useful agents for the treatment of PAH, asthma, and COPD. This article reviews the physiological significance of VIP in cardiopulmonary system and the therapeutic potential of VIP-based agents in the treatment of pulmonary diseases.
Highlights
Vasoactive intestinal peptide (VIP) is a 28-amino-acid peptide, which was first isolated from upper intestine, and has been characterized as a vasodilatory peptide [1]
Studies using VIP deficient animals and using animal models of diseases have indicated that VIP has significant therapeutic potential in the treatment of cardiopulmonary diseases, including pulmonary arterial hypertension (PAH), chronic obstructive pulmonary disease (COPD) and asthma [9,10,11]
This article describes the physiological significance of VIP and its therapeutic potential for the treatment of cardiopulmonary diseases, including PAH, asthma, and COPD
Summary
Vasoactive intestinal peptide (VIP) is a 28-amino-acid peptide, which was first isolated from upper intestine, and has been characterized as a vasodilatory peptide [1]. 8. Therapeutic potential of VIP in PAH The main pathological features of PAH in the pulmonary vasculature are perivascular inflammation, thrombosis, abnormal growth of vascular smooth muscle cells and extracellular matrix accumulation, leading to remodeling of the pulmonary vessel wall, obstruct pulmonary blood flow and cause right heart failure. Airway remodeling caused by airway inflammation includes an increase in airway wall thickness, fibrosis, smooth muscle mass and vascularity, as well as abnormalities in extracellular matrix composition [89,93] These shared pathological features suggest possible common underlying mechanism among PAH/ asthma/COPD. It is possible to envisage that development of controlled-release biodegradable VIP-based drug system, with airway delivery capability would have very significant therapeutic benefits in the treatment of cardiopulmonary diseases, including PAH, COPD and asthma
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