MMP9 Functions and Why it is Important
MMP-9 is one of a class of zinc-dependent enzymes called Matrix metalloproteinases (MMPs), which are involved in the body’s natural process of tissue repair and replacement. MMP-9‘s protein breakdown properties help stimulate the immune response that initiates development and may exacerbate disease progression.
Physiologically, MMP-9 plays a role in normal tissue growth and repair processes such as neurite growth, embryonic development, blood vessel creation, ovulation, wound healing, and bone formation .
With this in mind, it is easy to see why one would want to encourage MMP9 when there is an injury, and want to inhibit it when inflammation is out of control or when cancer development is underway.
MMP9 Destroys the Blood-Brain Barrier (BBB)
Inhibitors of MMPs have been shown to restore the Blood-Brain Barrier (BBB) integrity .
Conditions & Situations With Increased MMP9
All of the most common diseases have elevated MMP9, including a variety of autoimmune diseases, cancer, obesity, diabetes, and heart disease. This is because inflammation increases MMP9.
- Cancer (in the blood) – including Breast Cancer 
- Inflammatory diseases, includingCIRS (mold exposure)
- IBD (Crohn’s, Colitis) 
- Emotional Stress 
- Obesity – Higher MMP-9 levels are found in obese subjects [8, 9] and MMP-9 is correlated with BMI .
- Neuropathic pain – MMP9 is critical for neuropathic pain 
- Heart disease (atherosclerosis, etc…). In heart attack models, MMP-9-deficient mice showed reduced rupture rate.
- High blood pressure
- Arthritis – in affected tissue . The activation of MMP-9 production in tissue decreases collagen synthesis rates.
- Multiple sclerosis – lesions are correlated with MMP9 levels . In individuals experiencing an exacerbation of MS, MMP9 was found to be elevated in the spine . Furthermore, treatment with an MMP inhibitor halted the progression of MS in animal models .
- Alzheimer’s 
- Lupus (in the blood) 
- Sjogren’s (in tear-producing glands) 
- Systemic sclerosis (in the blood) 
- Polymyositis (MMP9 expression in certain tissue increased) 
- Growth & Development
- Wound healing
Conditions & Situations With Decreased MMP9
Supplements to inhibit MMP9:
- Curcumin[19, 20, 21]
- Resveratrol 
- Berberine 
- Tea/EGCG [24, 25]
- Andrographis 
- Fish oil (rats) 
- Forskolin 
- Ginger [29, 20]
- Magnesium 
- NAC (in test tube studies) 
- Glycine 
- Baicalin (rat model) 
- Ursolic acid 
- DIM 
- Adenosine (by neutrophils) 
- Capsaicin 
- Carnosine 
- Cranberry (flavonoids) 
- Proanthocyanidins (bilberry, green tea, black tea, black currant) 
- Apigenin (flavonoid) (mice) 
- Apple polyphenol (in test tube studies)
- Pomegranate 
- L-arginine 
- Grape seed extract
- Inositol 
- Astragalus and Panax Ginseng 
- Holy Basil/Tulsi (Ocimum sanctum) essential oil 
- Caffeine 
- Hydroxytyrosol 
- Broccoli 
- Watercress 
- Lycopene 
- Ecklonia cava 
- Angelica gigas/decursin 
- Boswellia/Frankincense (Boswellia frereana) 
- Chinese Hawthorn (Crataegus pinnatifida) 
- Matrine (alkaloid from plants of the pea family) 
- Nobiletin (a citrus flavonoid) 
- Silver (for wounds in test tube studies) 
Hormones to inhibit MMP9:
Pathways to Inhibit MMP9:
- Inducing tolerance of toxins 
- Interferon Gamma (Th1 cytokine) 
- PPARgamma 
- Nf-kB inhibitors 
- ACE inhibitors
- Angiotensin receptor inhibitors
- Aldosterone inhibitors
- TIMP-1 
- SIRT1 
- STAT3 inhibitors 
- AP-1 inhibitors 
Drugs to Inhibit MMP9:
- Atorvastatin , Pravastatin, and statins in general.
- Prednisolone 
- Doxycycline 
- Minocycline 
Activators of MMP9
MMP-9 is secreted by a wide number of cell types, including neutrophils, macrophages, and connective tissue cells. Macrophages (the scavenger type of white blood cells) are a potent source of MMP-9.
- Psychological, emotional stress and activation of the nervous system  – causes neutrophils to release MMP9.
- Fungal toxins (T-2 toxin) 
- Amyloid beta [67, 68]
- TGF beta1 
- VEGF  – MMP-9 also increases VEGF.
- NGF (potentiates) . MMP9 also potentiates nerve growth factor neurite growth 
- Angiotensin II (via Nf-kB, EGF and MAPK)
- Aldosterone(via NF-κB)
- Reactive oxygen species (ROS) (via NF-κB)
- TNF – especially potent
- Other MMPs, including MMP-2, -3, -13, -17, and -26
- Urokinase-type plasminogen activator (uPA)
- Tissue-type plasminogen activator
- Heat shock protein 60 (HSP60) (in white blood cells)
- Epidermal growth factor (EGF), basic FGF (connective tissue growth factor), PDGF (Platelet-derived growth) 
- All protein-degrading enzymes released from neutrophils promote MMP-9 activation
Supplement/Equipment Activators of MMP9
- IR/visible light spectrum of sunlight (in vivo) (74)
- Manganese and boron (in test tube studies) 
- Chitosan (enhanced activity of MMP-9 produced by macrophages with time) 
- Fucoidan increases TNF-alpha induced MMP-9 
Want More Targeted Ways to Combat Inflammation?
If you’re interested in natural and more targeted ways of lowering your inflammation, we at SelfHacked recommend checking out this inflammation wellness report. It gives genetic-based diet, lifestyle and supplement tips that can help reduce inflammation levels. The recommendations are personalized based on your genes.
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