What is Vasoactive Intestinal Peptide (VIP) peptide?
Studies highlight the role of VIP in controlling inflammation, especially in neurodegenerative disease, pulmonary fibrosis, inflammatory bowel disease, and cardiac fibrosis. The peptide is effective in the treatment of fibrosis. VIP is also a potent immune system regulator and general anti-inflammatory peptide. It is of active interest for its ability to preserve cognitive function in the setting of neurodegenerative disease.
Vasoactive intestinal peptide (VIP, vasoactive intestinal polypeptide, PHM27) is a short peptide hormone made in the gut, pancreas, and brain of most vertebrate animals, including humans. VIP binds to class II G protein-coupled receptors and is known to:
· Triggers the breakdown of glycogen in liver and muscle
· Reduces blood pressure
· Relaxes smooth muscle throughout the GI tract
· Triggers contraction of cardiac muscle
· Stimulates the secretion of water in the GI tract
· Influences vaginal lubrication
· Regulates prolactin release
· Protects cartilage
· Protects neurons against ischemia and oxidative stress
· Affects autonomic nerve function
· Synchronizes the central nervous system and regulates circadian rhythm.
AKA: PHM27, Vasoactive intestinal polypeptide
Molecular Formula: C147H237N43O43S
Molecular Weight: 3326.8 g/mol
CAS Number: 37221-79-7
VIP is synthesized from the immune nerve fibers in blood vessels of the central and peripheral nervous systems and immune cells. It reduces inflammation in inflammatory bowel diseases (IBDs) like Crohn’s and ulcerative colitis by suppressing the production of interleukin-10 and improving intestinal barrier function. Compromised barrier function leads to increased antigenic material in the space between cells, which interacts with immune cells to trigger an inflammatory response. VIP thus helps to reduce the antigen presentation to immune cells by improving the barrier function.
Vasoactive Intestinal Peptide in Lung Function
VIP impacts lung function through the following two pathways. The first mechanism alters pulmonary vascular remodeling in response to inflammation by suppressing a peptide called NFAT, which is known to activate T cells, leading to increased inflammation. In particular, NFAT suppression may play a very important role in preventing pulmonary fibrosis, the end stage of diverse inflammatory conditions such as COPD, sarcoidosis, etc.
Smooth muscle cell proliferation is one of the long-term consequences of lung inflammation and is a challenge in bronchial asthma that has been uncontrolled for extended periods. VIP is a potential molecule that inhibits smooth muscle proliferation.
Preliminary research shows that VIP lowers blood pressure in the pulmonary artery, leading to increased cardiac output and improved venous oxygen saturation.
VIP in Transplants
Rejection by the body’s immune system is one of the primary challenges faced in organ transplants. Currently, it is addressed through the use of broad-spectrum anti-inflammatory medications. Unfortunately, these medications can lead to susceptibility to serious infections and have side effects, such as scarring and organ fibrosis.
VIP affects dendritic cells (DCs). By reducing DC proliferation and activation, VIP helps suppress immune responses. Hence, VIP selectively inhibits the proliferation of DCs that might cause an autoimmune reaction. This could make VIP/VIP analog the foundation of transplant anti-rejection medicine in the future.
VIP as a Neuroprotectant
VIP plays a three-fold role in the central nervous system: neurotransmitter, neurotrophic/neurogenic, and anti-inflammatory/neuroprotectant. In this case, the peptide helps maintain the very critical function of the blood-brain barrier (BBB). Compromise of the BBB has been implicated in multiple sclerosis, encephalomyelitis, and even stroke.
VIP also offers neuroprotective function in Alzheimer’s disease and Parkinson’s disease. VIP acts as an important neuroprotectant in the developing brain. It helps ward off excitotoxic white matter damage and improves neuron fatty acid myelination.
The exact role of VIP in Alzheimer’s disease (AD) is less clear. Research shows that the processing of VIP is inhibited in AD, with levels of the peptide and amino acid byproducts being lower in the brains of people affected by AD.
The effect of VIP is mediated through VPAC1 and VPAC2 receptors. In both cases, stimulation results in increased secretion of neurotrophic factors like ADNP (activity-dependent neurotrophic factor) and BDNF (brain-derived neurotrophic factor). Both of these peptides help to protect synapses and astrocytes.
As with lung disease, fibrosis is the end stage of several cardiac conditions. Cardiac fibrosis leads to several serious problems, including valve dysfunction, decreases in contractility, changes in cardiac filling, and more. As in lung disease, cardiac fibrosis is the common end-stage of many heart conditions, thus requiring a transplant.
Research on rat models indicates that VIP may not only slow fibrosis down but can reverse scarring. This effect is partly mediated by a massive reduction in the expression of angiotensinogen and angiotensin receptor type 1a. This makes sense as angiotensin receptor blockers and ACE inhibitors have long been known to slow down cardiac modeling/fibrosis and are the first line of prevention for fibrosis.
Vasoactive Intestinal Peptide and COVID 19
A synthetic version of VIP called Aviptadil (RLF-100) may help to improve the lung complications in severe cases of Covid 19. Aviptadil, like VIP, inhibits pro-inflammatory cytokine production. This translates into protecting type-2 alveolar cells, the cells responsible for the bulk of oxygen exchange in the lungs. In fact, Aviptadil may actually block the SARS-2 coronavirus entry into alveolar cells.
Patients on ventilator and ECMO show remarkable recovery just three days after treatment with RLF-100. Any antiviral agent has not demonstrated the rapid recovery from infection and demonstrated inhibition of viral replication the way that Aviptadil has.
VIP is a member of a much larger group of neuro and endocrine peptides. It has been shown to affect the central nervous system, GI tract, pulmonary tissue, and immune system. It is known to play an active role in embryonic growth and development.
VIP has been found to regulate inflammation throughout the body, especially in neurodegenerative disease, pulmonary fibrosis, inflammatory bowel disease, and cardiac fibrosis.
The peptide is also a potent immune system regulator and general anti-inflammatory. It protects the central nervous system and preserves cognitive function in the setting of neurodegenerative disease.
Finally, synthetic variants of VIP have shown promise in treating COVID 19 and have been fast-tracked by the FDA for stage 2/3 clinical trials. This may ultimately prove beneficial for other VIP-related treatments and help pharmaceutical companies to invest in therapeutics. Innovation and research on vasoactive intestinal peptides will be one of the crucial focuses in the upcoming decade.