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Better Therapies For Cardiovascular Disease May Be Product Of Protein Tug Of War

Two proteins are in a tug of war that determines how much the body makes of superoxide, a highly reactive and potentially destructive product of oxygen that's dramatically elevated in cardiovascular disease, researchers report.
Their finding indicates an antiulcer drug just may help the body reduce excessive levels.
Hsp90 and Hsp70 are both heat shock proteins but appear to have opposite effects on reactive oxygen species production, said Dr. David J.R. Fulton, Interim Director of the Vascular Biology Center at the Medical College of Georgia at Georgia Health Sciences University.
"Our studies show that Hsp90 promotes the activity of Nox enzymes, the source of reactive superoxide and all of the reactive oxygen species that descend from it, while Hsp70 has an opposing action that inhibits Nox," Fulton said.
When researchers gave Hsp90 inhibitors, the binding of Nox enzymes to Hsp90 was reduced, its binding to Hsp70 increased and reactive oxygen species production decreased. The inhibitors also reduced reactive oxygen species production in blood vessels from obese mice, where it contributes to the loss of elasticity and narrowing that are hallmarks of cardiovascular disease. While Hsp90 inhibition was known to suppress inflammation and reduce cardiovascular damage, just how it made these positive changes was unknown.
The yin and yang the researchers found points toward a targeted therapy that should give Hsp70 the edge, said Dr. Feng Chen, postdoctoral fellow. Chen is first author of the study in the American Heart Association journal Arteriosclerosis, Thrombosis and Vascular Biology.
Hsp90 inhibitors are used to treat cancer, which depends on Hsp90 to support rapid cell division. But they also target proteins that help blood vessels relax, such as nitric oxide synthase, so probably are not a good choice in cardiovascular disease. "Cardiovascular disease is a chronic disease, and we want to minimize negative side effects while providing protection," Fulton said.
In this case, a better approach appears to be directly increasing the expression of Hsp70 with a drug such as geranylgeranylacetone, or GGA, an antiulcer drug used in Japan with relatively few side effects, Chen said. When the MCG researchers treated human aortic vascular smooth muscle cells with the drug, for example, Hsp70's binding to Nox increased while Nox's ability to generate superoxide decreased.
Next steps include looking at whether this increased expression of Hsp70 actually translates to healthier blood vessels in a cardiovascular model. "If we can upregulate Hsp70 without affecting nitric oxide synthase, it should," said Fulton, the study's corresponding author.
Hsp70 and 90 are chaperones that guide protein folding in different ways and can influence more than just whether Nox enzymes are stable or degraded. Hsp70 levels are regulated by the molecule heat shock factor, which is bound to and repressed by Hsp90. That's one reason why Hsp90 inhibitors increase Hsp70 levels.
Reactive oxygen species are not all bad, the researchers noted. At normal levels, they aid cell signaling and homeostasis as well as the mounting of an immune response. However, excessive levels associated with chronic inflammation are thought to accelerate cardiovascular disease. "A little bit is good; you want a well-honed immune system to fend of pathogens," Fulton said. "Chronic inflammation is the problem."
The researchers completed their studies in normal and diabetic mice - diabetes increases the risk of cardiovascular disease by at least 50 percent - as well as the saphenous, or major superficial leg veins, of patients with cardiovascular disease.

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'Protecting' Psychiatric Medical Records Puts Patients At Risk Of Hospitalization 'Switch' Critical to Wound Healing Identified 1811 2013 4 Ways to Beat Back Pain 5 hour energy 500 calories A simple soliloquy a1c AA aarp ablum accessible wheelchair car accessible wheelchair vans acne acne light treatment acting insulin acu acupressure ADD addiction ADHD adolescent victims adults Adults With Diabetes And Limited Health Literacy Less Likely To Adhere To Prescribed Antidepressants advance advise advising afghanistan Aflac Age Matters in Weight Gain: aids airsoft album review Alcoholic Alcoholics Anonymous All IT Supported alltel alzheimers AM General American College of Gastroneterology American Diabetes Association American Express ami clubwear amiclubwear.com amputation android anger animis anniversary anti radiation cell phone technology antibody antidepressants not working anxiety app application apps arginine arthritis artificial artistic aspirin Assurance Wireless asteroid 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diabetic shock diabetic software diabetic supplies diabetic. ebook diamonds diet digital camera digital logbook direct Direct Association Between Type 2 Diabetes And Obesity Found direct tv directionless dirve disability disabled disease disorders Disrupting Our Internal Clocks May Lead To A Complete Absence Of 24-Hour Bodily Rhythms And An Immediate Gain In Body Weight Ditto divorce lawyer diy mouse trap dlucose doctors donation doomsday Doughnuts down range Drexel University drinking drive drop out drug drug abuse drugs dry skin DSHS dvd e-cig e-cigarettes e-juice e-reader e-zines eastern medicine eating disorders ecigarettes Economics education Edward Norton effective treatments egg whites egg yolks electri vehicle electrical stimulation Electronic emergency emergency kit Emma Stone emotional employment empty nest EMR endocrine engraved medical id ereader ev everyone else eviction excess weight exercise exercise regularly exercise routines exterminators eye eye care eye disease eye glasses EyeBuyDirect eyebuydirect.com facebook fad diet fad diets family focused therapy Family Time fashion fatty acids favorite foods FDA feel fuller fire fish oil fitness Fitness Professionals Appreciate Online Continuing Education Options Fitness; Obesity; Diabetes; Molecular Biology; Mice; Biology flights florida Florida health kids program flu food Food and Dining food diary food network foods contain forgetfulness four more years free free android apps free diabetic wristband Free Stuff french fries fresh flowers fresh fruit Fresh Vending Machines fructose fructose corn syrup fruit full moon funeral Gadgets gangnam style Gastroesophageal gastroparesis GE X500 Power Series genes genes linked to bipolar GERD gestational diabetes Gestational Diabetes Patients Will Develop Type 2 Diabetes Give Aways giving glasses glooko glucagon Gluco(M) Glucofact glucose glucose levels glucose log glucose management glucose meter gluten free glycemic control glycemic foods glycemic index glycemic indexes godaddy google gout grain foods green tea group guest blog guest post hair loss handicap accessible vans handicap minivans handicap vans handicapped vans happy Happy Birthday Hello Cupcake It's Me happy birthday to me :) happy holidays Harvey Birdman hba1c health health benefits health care healthier fast food healthy healthy foods healthy lifestyle healthy snack hearing loss heart heart attack heart broken Heart Disease; Cholesterol; Stroke Prevention; Diseases and Conditions; Chronic Illness; Heart Disease; Cholesterol; Stroke Prevention; Diseases and Conditions; Chronic Illness; diabetes Heart Disease; Cholesterol; Stroke Prevention; Diseases and Conditions; Chronic Illness; stroke Heart Disease; Cholesterol; Stroke Prevention; Diseases and Conditions; Chronic Illness; Vioxx heart monitor heart on my sleeve heart problems heart rate heath and beauty hello hellocupcakeitsme.com help hemoglobin Her high blood sugar high school High-Fat Foods May Be A Factor In Glucose Control hiv hiv1 hiv2 hobbytron.com holiday holiday's home security alarms home testing Homeless Homeless Shelter Homer Simpson honda hospitalization Household Income Affects Chronic Disease Control In Kids Humalog Human IPSC Humor Humulin R U-500 hunger hungry hurt on the job hyperglycima hyperglycimic hypertension hypoglycemia hypoglycemic hypoglycemic episode iBGStar Blood Glucose Monitoring System Ice Cream Image improvement including mufa foods infection infested infographic information injury inspriation insulated bag Insulin insulin injections insulin patch insulin pump insulin shot record insurance claims internal medicine Interspecies Transplant investments ios ios 5 iphone iphone 4 its iTunes Iwerkz Foldable Bluetooth Keyboard Review Jenna Mables jewelry joann joann fabric and craft store joint pain Journal of Alzheimer's Disease juwait Keek kenguru ketoacidosis occurs kicking the habbit kid kidcare kids Killings kindle kindle fire kitchen counter kombucha Labor and Industry Lamp;I lantus Late-Life Depression lawyer learning issues legal help Lexapro LG Rumor libido life lifestyle changes light box lincoln Link Between Creativity and Mental Illness Confirmed in Large-Scale Swedish Study Lipohypertrophy living loan Lone Star College Shooting loneliness lose weight losing weight loss plan lost low blood sugar low glucose levels Low income cell phone low income glasses low t low testosterone lower glucose lowering lowering glucose levels Luminaze lung health lyrics lyrics of depression Mainframe Support makeup managing diabetes Manic marijuana market mary lambert Master Card maya angelou Maya Angelou dead at 86 me meal plan meal prepping meals require medflash media / television medicaid Medical medical condition medical help Medical Review Medical Studies medical studies. medicare medicare part d medication medicines meditation melody road memory loss men's health Mental Health mental health issues Menu menu options merry christmas metabolic syndrome metabolism metabolites metersync blue miami Michael Keaton microstimulator military minimum purchases mission d.a.d mission dad Mixed Results On Computer-based Support For Diabetes mobility money money saving moods motivation mourning movie review Movie Reviews music music thearpy musings/thoughts/ideas must have MV-1 n-3 Fatty Acids Nanoparticle Suspension and Ultrasound Deliver Insulin Without Regular Injections natural home remdies natural suppliments need needing help needles needy negative thoughts neil diamond Network/Community networking new app new baby New Jersey's Universtiy of Medicine and Dentistry new medication New smart contact lens could monitor glucose for diabetics Nick Jonas night lights nissan no insulin Nook Tablet BNTV400 Review north aferica nova nordisk Now that the holidays are over obama obama phone obama wins 2012 obese Obesity obituries OCD ODD Oil Pulling Olycap omega-3 onetouch online magazines online medical records optical zoom optical123.com Optimus ERM optogenetics oral health oral hiv test oral swab oraquick overcome depression Oxygen paid marketing pancreas parental depression parkinsons party passing Paula Deen pay attention payday payday advance paying kids to attend school pedometer personal food chart Personal Post pest pests photography pills ping plam beach county Plays poet port townsend positive thoughts Postpartum Depression pot prayer pre-owned pre-school pregnancies pregnancy prepper prepping preschool prescription president prevent complications prices processed foods product Product Review products Progress Project 1811 project rudolph proline promo codes promotional Promotions psoriasis Psy public health publich education purchas questioning quit smoking raisins reaching out real butter real-estate really scare rearrange recipes Record red meat red wine reefer reflux regenerate regular exercise rehab remodel research resistance resource resources retail therapy retinopathy revamp review Reviewing the Vapourlites Blueberry/Strawberry E Juice revitalift rich foods risk roller coaster russia rx s.a.d sadness safe sex safelink Safelink wireless sale salt Sandy Hooks Elementary School Schooting saving money savings scar school School Shooting schooling scrubs for cheap seasonal affective disorder Seattle self diagnosis self help self love self medicating senior resources seo sesame seed oil sex Shindigz Coupon Code Shootings shopping Short story shot record sick side-effects simple tips SIN TAX Site Review skin care skin tags skip meals skipping meals sleep sleep apnea smaller meals smart car smart cars smart phone smoker smokes smoking social media social security sodium software sore throat sores south beach south beach diet spiral notebook sponsored sponsored review sponsored; lawyer; family; legal; issues; sponsored/guest post spot removal. ssi Statin Labels stem cell stock pile stomach pain stoner stop smoking store stress stretch marks study submit submitted substitutions successfully lose weight sugar free sugar levels sugary foods suicidal thoughts suicide Supplementation Of Alternative Fuels Could Protect The Brain During Hypoglycemia support surgery survival systemic inflammation taboo tai chi take out tax tea tech teen teen mental health teens television temporary mood test animals test strips testicle testicular cancer testing testing supplies testosterone thanksgiving the learning company the lines project. #thelinesproject thearpy therapy thought Three Devastating Statistics of Diabetes Medical Malpractice title to write love on her arm tone Tosh.O toxins Tracfone trained professional transaction travel treatment trend diets tribute to my father triglycerides tsa tweets twitter twloha type 3 diabetes type-1 type-2 type-2 diabetes U.S. Medicare Part D Can't Explain North-South Disparities UK News ultra long acting UMDNJ underlying reasons Undiagnosed Pre-Diabetes Highly Prevalent in Early Alzheimer's Disease Study unhealthy unhealthy foods up and coming artist up and down upcoming holidays update uric acid usb value of a dollar vans for handicap vans for handicapped vans for wheel chairs mobility vans vans for wheenchairs vape vapor vapourlites vendor Veterans Day Video violation violence Visa Visiting Your Doctor Following ER Care For Chest Pain Reduces Risk Of Heart Attack vitamin d vitamin deficiency walking walking chart walnuts contain washington water waterski weed week in review Week of learning weigh yourself weighing yourself weight weight loss weight loss chart weight loss goals weight loss plan weight loss program weight loss success weight loss tips weight slowly what is it What Your Skin Says About Your Health wheel chair wheel chair vans wheelchair wheelchair vans where to buy cheap scrubs whipped butter winter blues womens health Work Out workman's compensation workout X-Men x500 xanax Xenotransplantation Young people with diabetes dying due to lack of adequate healthcare Yourtel youtube YouTube Internet Sensations Then and Now

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