University of Missouri School of Medicine MU Health School of Medicine
News Divider

Compound improves cardiac function in mice with genetic heart defect

MU study recognized by American Heart Association

Congenital heart disease is the most common form of birth defect, affecting one out of every 125 babies, according to the National Institutes of Health. Researchers from the University of Missouri recently found success using a drug to treat laboratory mice with one form of congenital heart disease, hypertrophic cardiomyopathy — a weakening of the heart caused by abnormally thick muscle. By suppressing a faulty protein, the researchers reduced the thickness of the mice’s heart muscles and improved their cardiac functioning.

Maike Krenz, MD, has been studying hypertrophic cardiomyopathy for nearly 10 years, soon after a gene was discovered in 2001 that linked the disease to the genetic conditions Noonan syndrome and LEOPARD syndrome. In Noonan and LEOPARD syndromes, the thickened heart muscle of hypertrophic cardiomyopathy is caused by a defective Shp2 protein, created by a mutation in the gene PTPN11.


“Previously, not much has been known about the biochemistry behind Shp2 and hypertrophic cardiomyopathy,” said Krenz, an assistant professor of medical pharmacology and physiology at the MU School of Medicine, and a researcher at MU’s Dalton Cardiovascular Research Center. “We know the thickened heart muscle is sick and doesn’t work properly, and we know a defective Shp2 protein can cause heart muscle to thicken. However, to create an effective treatment, we need to know what Shp2 is doing inside the heart to cause the defect.”

To test whether they could interrupt the heart’s hypersensitivity to growth signals, the researchers gave a chemical compound, PHPS1, to mice with a mutated gene that produces the defective Shp2 protein.

“Not only did the compound reduce the thickness of the heart muscle to the size of normal heart muscle, but it also improved the cardiac pumping of the heart,” Krenz said. “That’s important because people with hypertrophic cardiomyopathy have an increased risk of sudden cardiac death. If we could develop an effective treatment for the disease and improve patients’ heart function, we could save many people’s lives.”

Because of the role Shp2 plays in signaling heart growth, Krenz believes the research could be translated in the future into improved treatments for other types of heart disease, such as damage caused by heart attack.

Krenz presented the research findings, “Inhibition of Shp2’s Phosphatase Activity Ameliorates Cardiac Hypertrophy in LEOPARD Syndrome Models,” at the American Heart Association’s Scientific Sessions conference in November 2013, where it received the Outstanding Research Award in Pediatric Cardiology. LEOPARD syndrome is related to Noonan syndrome and receives its name from an acronym for multiple lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth and deafness.

Click here to download a high resolution portrait of Krenz.

MU Health Magazine


News and Events

Rural Track Pipeline Program MU School of Medicine Celebrates 20th Anniversary of Rural Track Pipeline Program
Aim is to address shortage of physicians in rural areas

Gerald Meininger, PhD Professor Recognized as International Leader in Microcirculation Research
Vascular health expert recently received prestigious Kitanomaru Award in Japan

Health Sciences Research Day MU Health Students, Faculty Receive Awards at Annual Health Sciences Research Day
Event features projects from student and physician researchers

Jane McElroy, PhD Resilience-based Interventions Could Curb Depression in LGBT Youths
Researchers suggest strategies to improve mental health of young people

Erika Ringdahl, MD MU Awarded $1.1 Million to Enhance Role of Primary Care Physicians
Program will train primary care doctors to create patient-centered medical homes

Quinn Johnson Johnson Named MU
Anesthesiology Chair

Clinician educator joined University of Missouri in 2010

Vogel Taking Cholesterol Medication Before Aneurysm Repair Improves Outcomes
Patients taking statins before endovascular aortic aneurysm surgery more likely to survive

Thakkar New Finding Helps Explain Why Many Alcohol Drinkers Also Are Smokers
Knowledge may help curb alcohol and nicotine addiction

Dongsheng Duan, PhD Gene Therapy Treats All Muscles in the Body in Muscular Dystrophy Dogs
Human clinical trials are next step, MU researchers say

Peter Konig, MD Test Catches Asthma in Children Before Symptoms Appear
Researchers find common pulmonary function test can help with early diagnosis

Media Relations
University of Missouri Health System
One Hospital Drive, DC028.00
Columbia, MO 65212
24/7 on-call pager: (573) 876-0708

Mary Jenkins
(573) 882-7299

Jeff Hoelscher
(573) 884-1608

Derek Thompson
(573) 882-3323

Diamond Dixon
(573) 884-7541

Justin Kelley (Photographer)
(573) 882-5786
Pager (573) 397-9289

Web Communications
University of Missouri Health System
One Hospital Drive, MA204G, DC018.00
Columbia, MO 65212
(573) 884-0298

Laura Gerding, APR
(573) 882-9193

Velvet Hasner
(573) 884-1115

Justin Willett
(573) 884-7740

Printer Friendly
Follow us on Twitter!   Facebook   YouTube Videos   Instagram   Pinterest  
Website created and maintained by the Office of Communications. Contact the MU School of Medicine.
Revised: February 04, 2014 - Copyright © 2014 - Curators of the University of Missouri. All rights reserved. DMCA and other copyright information. An equal opportunity/access/affirmative action/pro-disabled and veteran employer.