Anti-Inflammatory And Antioxidant Peptides Called ApoA-I Mimetic Peptides Derived From Tomato Extract Can Reduce Intestinal Inflammation Due To HIV
A new study by researchers from the University of California Los Angeles (UCLA) has found that ApoA-I mimetic peptides, a type of anti-inflammatory and antioxidant peptides derived from tomato extract can reduce intestinal inflammation related to being infected with HIV
There is a dire need for novel therapeutic strategies are to attenuate increased systemic and gut inflammation that contribute to morbidity and mortality in chronic HIV infection despite potent antiretroviral therapy (ART).
The main aim of this study was to use preclinical models of chronic treated HIV to determine whether the antioxidant and anti-inflammatory apoA-I mimetic peptides 6F and 4F attenuate systemic and gut inflammation in chronic HIV.
The team used two humanized murine models of HIV infection and gut explants from 10 uninfected and 10 HIV infected persons on potent ART, to determine the in vivo and ex vivo impact of apoA-I mimetics on systemic and intestinal inflammation in HIV.
Interestingly when compared to HIV infected humanized mice treated with ART alone, mice on oral apoA-I mimetic peptide 6F with ART had consistently reduced plasma and gut tissue cytokines (TNF-α, IL-6) and chemokines (CX3CL1) that are products of ADAM17 sheddase activity. Oral 6F attenuated gut protein levels of ADAM17 that were increased in HIV-1 infected mice on potent ART compared to uninfected mice.
Adding oxidized lipoproteins and endotoxin (LPS) ex vivo to gut explants from HIV infected persons increased levels of ADAM17 in myeloid and intestinal cells, which increased TNF-α and CX3CL1. Both 4F and 6F attenuated these changes.
The preclinical data suggest that apoA-I mimetic peptides provide a novel therapeutic strategy that can target increased protein levels of ADAM17 and its sheddase activity that contribute to intestinal and systemic inflammation in treated HIV. The large repertoire of inflammatory mediators involved in ADAM17 sheddase activity places it as a pivotal orchestrator of several inflammatory pathways associated with morbidity in chronic treated HIV that make it an attractive therapeutic target.
It should be noted that apoA-I mimetic peptides could also be of use in both COVID-19 infections and also long COVID issues but warrants further research.
The study findings were published in the peer reviewed journal: PLOS Pathogens.
The study findings suggest that adding a certain type of tomato concentrate to the diet can reduce the intestinal inflammation that is associated with HIV. Left untreated, intestinal inflammation can accelerate arterial disease, which in turn can lead to heart attack and stroke.
The study findings provide clues to how the altered intestinal tract affects disease-causing inflammation in people with chronic HIV infection, suggesting that targeting the inflamed intestinal wall may be a novel way to prevent the systemic inflammation that persists even when antiviral therapy is effective in controlling a person's HIV.
Senior author, Dr Theodoros Kelesidis, an associate professor of medicine in the division
of infectious diseases, David Geffen School of Medicine at UCLA told Thailand Medical News
, “It is already known that inflammation is an important process that protects the body from invading infections and toxins. But in individuals who are successfully treated for HIV to the point that their viral load is no longer detectable, the continuing low-grade inflammation in the cells of the intestine contributes to an increased risk of heart attack or stroke.”
Dr Kelesidis added., “Individuals with HIV have been found to have a condition called "leaky gut," in which products in the gut bacteria, such as lipopolysaccharides, move to other parts of the body through the bloodstream. Those products promote systemic inflammation and can accelerate coronary disease.”
The study team worked with mice that had been infected with HIV and whose immune systems had been altered to mimic those of humans. The mice were fed a diet containing the tomato concentrate Tg6F, while the rest were fed a normal diet for mice ie. low in fat, cholesterol and calories.
The tomato concentrate Tg6F comes from a specific type of genetically modified tomato; it contains anti-inflammatory and antioxidant peptides called apoA-I mimetic peptides, which imitate the main protein in HDL, the so-called "good cholesterol."
The study team examined proteins called cytokines and chemokines that are known to predict intestinal and blood inflammation, which can augur adverse outcomes for people with chronic HIV infection.
The team found that mice that were given Tg6F had lower levels of pro-inflammatory cytokines and chemokines in their gut and blood than the mice that received the standard diet. In addition, they discovered that Tg6F prevented an increase in levels of a protein called ADAM17, which orchestrates inflammatory responses in people with chronic HIV infection. The investigators confirmed the anti-inflammatory effects of apoA-I mimetics in gut biopsies from people with HIV.
Dr Kelesidis added, "Targeting the inflamed intestine with the peptide that mimics the main protein in HDL may be a way of preventing systemic inflammation in people with chronic HIV. Giving oral apoA-I mimetics together with oral antivirals may be an attractive novel therapy to treat inflammation and prevent disease and death in HIV."
The study team however notes that mice cannot fully recreate all aspects of humans' HIV infection. Also, the gut biopsies used to test the effects of apoA-I mimetics do not fully reflect how inflammation works within a living human body.
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