Breaking News
April 18, 2019 - New gene therapy cures babies with fatal ‘Bubble Boy’ disease
April 18, 2019 - No female mice? Scientists may still approve NIH grant
April 18, 2019 - What needs to be said about mental health in medicine
April 18, 2019 - Hickenlooper Expanded Medicaid, Created State-Run Marketplace To Insure Nearly All Coloradans
April 18, 2019 - Cancer cells grown in tumor-mimicking environment can help predict the effect of experimental drugs
April 18, 2019 - Albireo Announces FDA Clearance of IND to Commence Phase 2 Trial of Elobixibat for the Treatment of NAFLD/NASH
April 18, 2019 - Adhesive gel bonds to eye surface, could repair injuries without surgery
April 18, 2019 - The future of genomics: A podcast featuring Stanford geneticists
April 18, 2019 - As Syphilis Invades Rural America, A Fraying Health Safety Net Is Failing To Stop It
April 18, 2019 - APOE gene impacts sleep depending on gender and severity of Alzheimer’s
April 18, 2019 - PCORI’s newly approved awards focus on cancer pain and opioid use disorders
April 18, 2019 - New tool provides a standard way to measure effects of caring for survivors of TBI
April 18, 2019 - Smartphone use risks eye examination misdiagnosis
April 18, 2019 - How drug-resistant bugs grow in CF patients’ lungs
April 18, 2019 - Gordana Vunjak-Novakovic Elected to American Academy of Arts & Sciences
April 18, 2019 - Podcast: KHN’s ‘What The Health?’ You Have Questions, We Have Answers
April 18, 2019 - Diabetic drug shows potential to be repurposed as heart disease treatment for non-diabetic patients
April 18, 2019 - New estimation method assesses natural variations in sex ratio at birth
April 18, 2019 - UTA scientist receives $1.17 million grant for cancer research
April 18, 2019 - Coagulation factor VIIa prevents bleeds in hemophilia animal models
April 18, 2019 - Researchers identify risk factors for severe infection after knee replacement
April 18, 2019 - Mass drug administration can offer community-level protection against malaria
April 18, 2019 - FDA’s added sugar label could have substantial health and cost-saving benefits
April 18, 2019 - Researchers identify cause of inherited metabolic disorder
April 18, 2019 - Single strip of white paint not sufficient to protect people who ride bikes
April 18, 2019 - Partner status influences link between sexual problems and self-efficacy in breast cancer survivors
April 18, 2019 - Colorectal Neoplasia Risk Up for Hodgkin Lymphoma Survivors
April 18, 2019 - Rigid spine muscular dystrophy – Genetics Home Reference
April 18, 2019 - Simple bile acid blood test could tell risk of stillbirth
April 18, 2019 - Center for Experimental Therapeutics aims to enable all steps of drug development | News Center
April 18, 2019 - Falling for telephone scams could be an early sign of dementia
April 18, 2019 - Researchers annotate key neuronal proteins in lamprey genome
April 18, 2019 - Study uncovers new biomarker for personalized cancer treatments
April 18, 2019 - Scientists enter research collaboration to find a cure for cancer
April 18, 2019 - Study to compare benefits of tai chi and mindfulness meditation on MS symptoms
April 18, 2019 - Gestational diabetes during pregnancy may increase risk of type 1 diabetes in children
April 18, 2019 - Is a New Remedy for Body Odor on the Horizon?
April 18, 2019 - Orthostatic hypotension – Genetics Home Reference
April 18, 2019 - Healing the heartbreak of stillbirth and newborn death
April 18, 2019 - Conference to highlight advances in human immune monitoring, bioinformatics | News Center
April 18, 2019 - Bacteria use viruses for self-recognition, study reveals
April 18, 2019 - New adhesive patch could help reduce post-heart attack muscle damage
April 18, 2019 - Researchers analyze the effects of dark play in a serious video game
April 18, 2019 - Scientists revive pig brain cells four hours after death
April 18, 2019 - Filial cannibalism and offspring abandonment may be forms of parental care
April 18, 2019 - Two proteins act in concert to maintain a healthy heart in mice, shows study
April 18, 2019 - Scientists create a functioning 3D printed heart
April 18, 2019 - Non-invasive vagus nerve stimulation improves disease symptoms in patients with rheumatoid arthritis
April 18, 2019 - Majority of men struggle to understand diagnosis and treatment of prostate cancer
April 18, 2019 - Researchers create new small molecules that may combat equine encephalitis viruses
April 18, 2019 - Animal-assisted therapy improves social behavior in patients with brain injuries
April 18, 2019 - Some viruses help protect harmful bacteria in CF patients | News Center
April 18, 2019 - Outpatient healthcare providers inappropriately prescribe antibiotics to 40% of patients
April 18, 2019 - Men who have a resting heart rate of 75 bpm are twice as likely to die early
April 18, 2019 - Novel serum biomarkers to detect NAFLD-related fibrosis
April 18, 2019 - New study delves deeper into individual genomic differences than ever before
April 18, 2019 - Gilead and Galapagos Announce Filgotinib Meets Primary Endpoint in the Phase 3 FINCH 3 Study in Methotrexate-Naïve Rheumatoid Arthritis Patients
April 18, 2019 - Emotional mirror neurons found in rats
April 18, 2019 - Sylvia Plevritis appointed chair of biomedical data science | News Center
April 18, 2019 - Cervical cancer subtype increasing in several subpopulations of women
April 18, 2019 - Yeast strain provides manufacturing boost to low-calorie sweetener derived from lactose
April 18, 2019 - One in five children and youth suffer from a mental disorder
April 18, 2019 - Improper inhaler use common in children with asthma
April 18, 2019 - C-Path and CDISC release global Therapeutic Area Standard for HIV research
April 18, 2019 - Integrating AI to analyze imaging data allows early recognition of heart disease
April 18, 2019 - Low-cost, high-speed algorithm may allow animal-free chemical toxicity testing
April 18, 2019 - HPV-negative cervical cancers are more aggressive with worse prognosis
April 18, 2019 - AI detects prostate cancer with same level of accuracy as experienced radiologists
April 18, 2019 - Study resolves sex differences in psychiatric illness risk
April 18, 2019 - Novartis Announces FDA Filing Acceptance and Priority Review of Brolucizumab (RTH258) for Patients with Wet AMD
April 18, 2019 - Cocktail of common antibiotics can fight resistant E. coli
April 18, 2019 - Persis Drell to give keynote address at medical school diploma ceremony | News Center
April 18, 2019 - EpicTogether: Remembering Our Why
April 18, 2019 - Study identifies novel loci contributing to asthma susceptibility in adults
April 18, 2019 - Gut bacteria and pregnancy
April 18, 2019 - New study finds that screening could help prevent rare types of cervical cancer
April 17, 2019 - Spatial orgnization of the genome can be altered using small molecules
April 17, 2019 - AEDs Tied to Higher Pneumonia Risk in Alzheimer Patients
April 17, 2019 - Telemedicine tied to more antibiotics for kids, study finds
April 17, 2019 - Two medical students awarded 2019 Soros Fellowships for New Americans | News Center
Restoring this enzyme’s function protects against heart disease in lupus and beyond

Restoring this enzyme’s function protects against heart disease in lupus and beyond

image_pdfDownload PDFimage_print
Restoring this enzyme's function protects against heart disease in lupus and beyond
Dr. Jim Oates (left) and Dr. Joy Buie (right) of the Medical University of South Carolina. Credit: Sarah Pack, Medical University of South Carolina

Patients with lupus, an inflammatory disease in which the body’s immune system attacks its own tissues, are on average seven to nine times more likely to develop heart disease than the general population. Younger women with lupus are 50 times as likely to develop the disease as young women without the disease.

The endothelium—the single layer of cells lining blood vessel walls—is thought to protect against heart disease. It does so in part by producing nitric oxide.

A research team at the Medical University of South Carolina has shown that the enzyme responsible for nitric oxide production stops working properly when exposed to serum from lupus patients. They also showed that its ability to produce nitric oxide can be restored by administration of L-sepiapterin. Their findings are published in an article published ahead of print by Lupus Science & Medicine.

The article provides proof of concept that the enzyme could be a therapeutic target for heart disease in lupus. Restoring the enzyme’s function could also help protect lupus patients against kidney disease. The same inflammatory forces are at work there but the damage occurs much more quickly.

The findings also suggest that restoring the protective function of endothelial cells could be a strategy for treating heart disease more broadly.

“Our study demonstrates that therapies directed towards restoring the function of the enzyme that makes nitric oxide might be effective in restoring the function of the endothelium,” explains Jim C. Oates, M.D., senior author on the article. Oates is director of the Division of Rheumatology & Immunology and vice chair for research at MUSC.

“So it’s a proof of concept that allows us to move forward in studying the enzyme, nitric oxide synthase, or restoring its function as a target for vascular disease in lupus,” continues Oates.

“This is a first step in a long process of trying to identify therapeutics that might be useful for preventing this accelerated phenotype of cardiovascular disease in lupus patients,” says Joy Buie, Ph.D., MSCR, a postdoctoral fellow at MUSC and the first author on the article.

For the study, the team collected serum samples from a cohort of African American patients, specifically Gullah patients, with lupus who have been followed since 2003. The South Carolina Clinical & Translational Research Institute at MUSC helped the research team collect study samples from control volunteers, process study samples from both study patients and control volunteers, and securely store collected data.

The MUSC team showed that exposing endothelial cells to serum from patients with lupus caused the enzyme that produced nitric oxide to quit working properly. That enzyme is known as endothelial nitric oxide synthase.

Instead of producing the protective nitric oxide, it began producing superoxide, which promoted damaging inflammation.

In essence, the enzyme lost its power to protect against heart disease and instead promoted conditions that could lead to it. A co-factor needed for the proper function of the enzyme had been rendered unusable by exposure of the endothelial cells to the serum of lupus patients.

Administering L-sepiapterin to the cells restored the enzyme’s ability to produce nitric oxide by providing a new and more reliable source of that co-factor.

“If you try to give the co-factor itself, it’s rapidly oxidized by the same process that leads to the dysfunction of the enzyme,” explains Oates. “So giving L-sepiapterin, a precursor to the co-factor, makes it less susceptible to that rapid breakdown.”

L-sepiapterin is not currently approved for administration in humans. However, it is under investigation for the treatment of a number of diseases, including diabetic gastroparesis. Before it can be administered to patients, much further testing, both in animal models and in clinical trials, will be necessary to confirm its efficacy and safety profile.

But these findings point to a whole new way of understanding, preventing, and treating heart disease, one that is not limited only to patients with lupus.

“Many people focus on controlling cholesterol to protect against heart disease,” explains Buie. “Our study focuses the attention on making endothelial cells happy and functional. It identifies therapeutic targets on endothelial cells as being important.”

That’s not to say that controlling cholesterol and other lifestyle changes aren’t important. They too can affect how well the endothelium protects against heart disease.

“Lifestyle modifications can affect the endothelium. The Western diet—characterized by highly processed foods that are high in saturated and trans fat and low in good oils like omega-3 fatty acids—contributes to heart disease in everybody, not just lupus patients,” explains Oates. “So changing to a healthy diet and becoming more active goes a long way.”

But these findings suggest that pharmaceutically restoring endothelial function deserves further study as an additional therapeutic approach for patients with lupus and others at high risk of heart disease.


Study reveals early warning signs of heart problems in patients with newly diagnosed lupus


More information:
Joy N Jones Buie et al, L-sepiapterin restores SLE serum-induced markers of endothelial function in endothelial cells, Lupus Science & Medicine (2019). DOI: 10.1136/lupus-2018-000294

Provided by
Medical University of South Carolina

Citation:
Restoring this enzyme’s function protects against heart disease in lupus and beyond (2019, March 25)
retrieved 17 April 2019
from https://medicalxpress.com/news/2019-03-enzyme-function-heart-disease-lupus.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.

Tagged with:

About author

Related Articles