Cardiovascular Experimental Imaging and Therapeutics

Mission Statement

To develop and evaluate innovative technologies that enhance our ability to diagnose and treat atherosclerosis.

Projects

Nanoparticles for Molecular Imaging of Atherosclerosis
In collaboration with researchers at The University of Texas MD Anderson Cancer Center, we have developed a nanoparticle for detecting atherosclerotic plaques. This nanoparticle extends the capabilities of existing technologies, such as image enhancement, magnetic resonance imaging, ultrasound, and nuclear medicine. Our long-term objective is to develop a noninvasive, cost-effective, simple, and widely accessible imaging tool for earlier detection of atherosclerotic plaques by altering existing technologies.

What is atherosclerosis? Atherosclerosis is a disease in which plaque (fat, cholesterol, calcium and other substances) builds up inside your arteries. Arteries are blood vessels that carry oxygen-rich blood to your heart and other parts of your body. Over time, plaque hardens and narrows your arteries, limiting the blood to your organs and other parts of your body.

Therapeutic RNAi
Ribonucleic acid (RNA) is an intermediate molecule in the gene expression pathway in cells. RNA interference (RNAi) is a process by which scientists can manipulate RNA molecules to treat atherosclerosis by inhibiting genes involved in the development and progression of atherosclerosis. RNAi is a rapidly evolving technology that offers tremendous potential in the treatment of atherosclerosis. The figures below demonstrate a Watanabe rabbit aorta with atherosclerotic plaque. 

Transmission electron microscope analysis shows that liposomes are accumulated in lipid rich areas within the atherosclerotic plaque of aorta tissue. (Fig. A). 

Deconvolution fluorescence microscopy image of an atheroma containing rhodamine-labeled liposomes (Li), green: liposomes. (Fig. B). 

Our aim is to knock down the marker protein in an effort to inhibit the atherosclerotic disease process using our liposome delivery system with our RNAi technology.

What is a liposome? A liposome is a tiny bubble (vesicle), made out of the same material as cell membrane. Liposomes can be filled with drugs, and used to deliver drugs to treat diseases.

Diagram depicting liposomes as small spherical particles composed of a phospholipid bilayer with an internal aqueous core. The hydrophilic core of liposomes is impermeable to hydrophobic molecules providing a protected delivery of selected compounds (yellow sphere) across the cell membrane. The lipid layer can be modified with antibodies or molecules (purple oval) to improve targeting capability.  [B. Walton, unpublished data]

Molecular Imaging
 We are working on combining existing imaging technologies to evaluate the efficacy of treatments and monitor the progression and remission of atherosclerosis. We have collaborated with Texas A&M University to develop technologies that could be used to screen patients for particular plaque types by identifying the biochemical composition, thus identifying unstable plaques that put patients at risk for an acute event.

Department Staff

• Brian L. Walton, MD, FACC – Director 
• Siqin Zhaorigetu, PhD – Research Associate
• Rosie Munoz, RVT – Senior Research Coordinator

Presentations

View a presentation by Dr. Walton at THI Grand Rounds:
"Imaging and Therapeutics for atherosclerosis and angiogenesis"

Recent Publications (2003-2011)

Walton BL.  Book review of Peripheral Arterial Disease: Diagnosis and Treatment edited by JD Coffman and RT Eberhardt.  Tex Heart Inst J 2003; 30:164.

Walton BL, Dougherty K, Mortazavi A, Strickman N, Krajcer Z.  Percutaneous intervention for the treatment of hypoplastic aortoiliac syndrome.  Catheter Cardiovasc Interv 2003; 60 (3)329-334.

Kar B, Butkevich A, Civitello A, Nawar M, Walton B, Messner G, Gregoric I, Feldman J, Myers T, Gemmato C, Delgado R.  Hemodynamic support with a percutaneous left ventricular assist device during stenting of an unprotected left main coronary artery.  Tex Heart Inst J 2004; 31:84-6.

Wilson JM, Walton B.  Lesions and lipids and radicals--O my!
Tex Heart Inst J. 2004; 31(2):118-26.

Walton BL. Lipid oxidation, lipoprotein-associated phospholipase A2, and acute coronary syndromes.  Acute Coronary Syndromes 2005; 7(2)42-46.

Walton BL, Leja MJ, Vickers VC, Fernandez ME, Sanguino A, Wang E, Clubb Jr., Morrisett J, Lopez-Berestein G Delivery of Negatively Charged Liposomes into the Atheromas of Watanabe Heritable Hyperlipidemic Rabbits. Journal of Vascular Medicine 2010; 15(4):307-13.

Cheema Z, Davies M, Reardon M, Walton, B. Hybrid Imaging to Facilitate Accurate  Placement of a Tevar  prior to Completion Esophagectomy. J Vasc Surg, Feb. 2011

Zhaorigetu S, Yang Z, Toma Ian, McCaffrey A. T and Hu CAA. (2011) Apolipoprotein L6, induced in atherosclerotic lesions, promotes apoptosis and blocks beclin1- dependent autophagy in atherosclerotic cells. J Biol Chem. 286:27389-7398.

Zhaorigetu S, Wan G, Kaini R, Jiang Z, Hu CAA. (2008) ApoL1, a BH3-only lipid-binding protein, induces Autophagic cell death. Autophagy 4:1079-1082.

Wan G, Zhaorigetu S, Liu Z, Kaini R, Jiang Z, Hu CAA. (2008) Apolipoprotein L1, a novel Bcl-2 homology domain 3-only lipid-binding protein, induces autophagic cell death. J Biol Chem. 283:21540-1549.

Hu CAA, Bart WD, Zhaorigetu S, Khalil S, Wan G, Valle D. (2008) Functional genomics and SNP analysis of human genes encoding proline metabolic enzymes. Amino Acids 35(4):655-664.

Links

RNAi Center at MD Anderson
www.mdanderson.org/rnacenter

Research Support 

• Co-investigator on a recently awarded RO1 grant in collaboration with Texas A&M Biomedical Engineering “Morphological and molecular imaging system for in-vivo atherosclerosis research.
• Principle Investigator MacDonald Research Fund. "Mechanisms of anionic liposome absorption in atherosclerosis plaque.”

Contact Information and Location

Cardiovascular Experimental Imaging and Therapeutics
Brian Walton
E-mail: bwalton@texasheart.org
Rosie Munoz
E-mail: rmunoz@texasheart.org

Phone: 832-355-9985

Mailing address:
6770 Bertner Ave.
MC 2-255 
Houston, TX 77030