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  • Resveratrol Inhibits Sight-Threatening New Blood Vessels At the Back Of The Eyes While Simultaneously Promoting New Blood Vessels That Repair The Heart After A Heart Attack

    August 29, 2014: by Bill Sardi

    There is a clear dichotomy in the treatment of patients who battle the loss of their vision due to wet (neovascular) macular degeneration while simultaneously attempting to mend scarred muscle tissue after a heart attack.

    This may be a greater problem than realized as ophthalmologists who commonly instill anti-growth factor drugs (anti vascular endothelial growth factor or anti-VEGF drugs) directly into the eye to induce abnormal blood vessels to recede may be completely unaware how many of their retinal degeneration patients have had a heart attack that requires the formation of new blood vessels to heal scarred muscle tissue.

    One study showed that the prevalence of early-stage macular degeneration was only 7.3% among patients age 50-64 years of age but was 54.5% among patients who had experienced a prior heart attack. [Current Eye Research Feb 2012]

    Few published reports recognize this therapeutic dichotomy.  Swiss researchers confirm that repeated instillation of anti-growth factor drugs (Lucentis, Avastin) into the eye play a key role in preventing permanent vision loss but since VEGF is a precursor for nitric oxide, a transient gas that is required to widen (dilate) blood vessels and to maintain circulation in the heart, “it can be argued that the beneficial effects of VEGF antagonism in the eye may come at the cost of adverse system effects, particularly after heart attacks and strokes.” [Current Hypertension Reports Feb 2010]

    One study does show a small but statistically significant increase in the likelihood for a fatal or non-fatal heart attack among patients being treated with anti-VEGF drugs (1.9 per 100 patients versus 0.8 per 100 patients over 12 months). [Retina May 2013]

    But that isn’t the precise issue that needs to be addressed among patients battling vision loss who are simultaneously attempting to mend their scarred hearts.  The question is whether repair mechanisms in the heart are being impaired by the use of anti-VEGF drugs in the eyes, not if anti-VEGF agents are causing heart attacks.

    For now, anti-VEGF drugs have been given a clean bill of health in regard to any alleged increased risk for a heart attack.  Some studies do not show any increased risk for a heart attack following Lucentis/Avastin treatment in the eyes. [Graefe’s Archives Clinical Experimental Ophthalmology Feb 2011; Archives Ophthalmology Oct 2010], though these studies are not large enough to truly dismiss any increased cardiovascular risk. [Journal American Medical Assn. Ophthalmology July 2014]

    Eye physicians are concerned and have investigated whether there are more blood clotting problems such as strokes or heart attacks following anti-VEGF therapy in the eyes but have not addressed the issue of impaired tissue repair in the heart among post heart attack patients. [Current Vascular Pharmacology Sept 2011]

    Heart researchers have demonstrated that VEGF reduces the size of an experimentally-induced heart attack. [PLoS One Feb 26]  Provision of VEGF to rodents improves the survival of regenerative heart stem cells in experiments conducted in the animal lab. [Nanomedicine June 15, 2014] So while anti-VEGF drugs may not cause heart attacks one wonders if they increase their severity.

    Actually oxidants (reactive oxygen species) drive the formation of new blood vessels in the heart (what is called neovascularization or angiogenesis).  Oxygen deprivation in heart or complete blockage of circulation due to a clot or collapsed artery induces growth factors (VEGF) that encourage the outcropping of new blood vessels in what is called collateral circulation in the involved area.  Restoration of blood supply to the oxygen-deprived tissue prevents death of heart muscle and subsequent scarring.

    The red wine molecule resveratrol, being both an antioxidant and pro-oxidant, has been identified as a stimulant to induce new blood vessel growth in the heart. [Antioxidants Redox Signaling. Nov 2006]

    Pre-treatment of animal hearts with resveratrol increases nitric oxide and promotes new blood vessel formation following a heart attack.  [Cell Biochemistry Biophysics 2006] Resveratrol has been demonstrated to reduce the size of a heart attack (area of scar tissue) and the number of heart muscle cells that die off after the event via its ability to increase VEGF and nitric oxide. [Vascular Pharmacology April 2005; Journal Molecular Cell Cardiology Nov 2005]

    Evidence that resveratrol promotes VEGF in the heart is contrasted by reports showing resveratrol inhibits VEGF and neovascularization/ angiogenesis in the retina. [Aging & Disease April 1, 2014; Journal Nutritional Biochemistry July 4, 2014]

    Puzzlingly, resveratrol and a commercially available resveratrol-based dietary supplement (Longevinex®) were shown to protect the heart during and after experimentally induced heart attacks in animal hearts by their “potent anti-angiogenic” action (ability to activate anti-VEGF genes). [Journal Cellular Molecular Medicine Oct 2012; PLoS One Dec 23, 2010]

    The therapeutic contradiction of whether to promote or inhibit VEGF among post heart attack patients with wet macular degeneration is resolved by resveratrol, which appears to exert both anti-growth factor properties in human eyes while simultaneously promoting new blood vessels in the heart.

    This therapeutic puzzle does not remain theoretical.  A resveratrol-based dietary supplement has been successfully used to subdue unremitting cases of wet macular degeneration that did not respond to conventional anti-VEGF drug treatment. [Nutrients June 4, 2013]  The nutraceutical used in this human application uniquely does not exert pro-oxidant action at high doses like plain resveratrol does and unlike resveratrol is non-cytotoxic (non-celling killing) in high-dose concentration. [Experimental Clinical Cardiology 2010]  It exerts 6-fold greater inhibition of microRNA that genetically control VEGF [PLoS One Dec 23, 2010] which may be why it worked when anti-VEGF agents given by direct instillation did not.

    Resveratrol also works to protect the heart via other mechanisms, namely by inhibiting blood clots (blood platelet activation); [Applied Physiology Nutrition & Metabolism June 2011]; by working as a metal (copper) chelator (key-lay-tor) [Biochemical Pharmacology May 1997]; by control of cholesterol [Molecular Cell Biochemistry Feb 2011]; by reduction of calcium influx into cells [Molecular Medicine Reports Aug 14, 2014]; by increasing the ability of living tissues to withstand oxygen deprivation [Molecular Medicine Reports Aug 10, 2014]; by its ability to dampen inflammation [Molecular Medicine Reports June 2014]; and by stimulation of protective internal antioxidant enzymes (catalase, superoxide dismutase, glutathione) via the Nrf2 gene transcription factor [PLoS One July 22, 2013].

    Resveratrol-based nutraceuticals may be considered among cases where ways must be found among post-heart attack patients with wet macular degeneration to simultaneously inhibit growth factors that threaten their vision in the back of their eyes and promote growth factors to promote healing and circulation in the heart.  ©2014 Bill Sardi,

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