Dr. Gopi Kolluru presented his talk entitled “The Role of Cystathionine Gamma Lyase and Endothelial Nitric Oxide Synthase for Cardiovascular Homeostasis” at the second American Gasotransmitter Symposium held in Eugene, Oregon from May 18-19, 2019.

My research is focused to identify the molecular signaling mechanisms involved in oxidative stress, and vascular growth and remodeling during cardiovascular pathology. I have been working towards bridging basic and clinical research for therapeutic revascularization in vascular diseases over the past 14 years. During my postdoc, I have examined the role of gasotransmitters NO and H₂S, including the role of cystathionine gamma-lyase (CSE) in regulation of ischemic vascular remodeling. We aim to identify the regulation of gasotransmitters (NO and H₂S) and associated signaling involved in vascular and metabolic functions in aging cardiovascular system, diabetes and pregnancy complications including preeclampsia. We approach this with the aid of diseased/transgenic mouse models, advanced analytical and non-invasive imaging techniques.

CSE/H2S role in vascular remodeling

Nitric oxide (NO) and hydrogen sulfide (H₂S) are two key gaseous signaling molecules, also called “gasotransmitters” that regulate key biological functions. Both these molecules are cardioprotective with their ability to regulate the vascular tone, blood pressure, and vascular growth and remodeling. Genetic deficiency of either endothelial NO synthase (eNOS) or cystathionine γ-lyase (CSE), enzymes that synthesize NO and H₂S respectively, has detrimental effects on tissue vascularization and vascular repair. VEGF demonstrates a crucial role in revascularization including endothelial progenitor cells (EPC) homing under ischemia. Severe impairment of CSE/H2S levels led to significant reduction in VEGF causing impaired angiogenesis, collateral formation. Impaired vascular growth and remodeling can be rectified VEGF levels that is rectified by H2S therapy via NO signaling pathway. Primary focus of our lab is to understand the mechanisms underlying vascular remodeling under cardiovascular disease.

Diabetes metabolism and vascular remodeling

Diabetes, is a metabolic disorder characterized by high blood glucose levels. Increased prevalence of diabetes and obesity can lead to severe complications in multiple organs and exacerbate complications including PAD, stroke, renal disease, pregnancy complications and nerve damage.  Our lab is focused in studies involving signaling mechanisms that can facilitate early identification and alleviation of disease processes, with drugs or therapeutics could enhance protection against diabetes and associated complications and risk factors. Specifically, we focus to identify the regulatory role of NO/H₂S and associated signaling mechanisms under diabetes complications.

Aging and Cardiovascular function

Aging is a biological process that causes progressive degeneration of the structure of all the organs subsequently their function. It is a major risk factor for cardiovascular diseases, and is associated with complications including oxidative stress and inflammation. As age progresses there is an increased prevalence of comorbidities including hypertension, ischemic cardiovascular disease, peripheral vascular disease (PVD), stroke, cancer and diabetic complications. Several factors are involved in aging – increased oxidative stress that contribute to vascular stiffening, reduced wound healing and angiogenesis due to loss of endothelial function. Our lab is interested to study age-dependent metabolism and dysfunctions in relation to H₂S/NO and associated signaling in aged mice.

Book Chapters

1. Kolluru GK, Yuan S, Kevil CG. H2S regulation of nitric oxide metabolism. Hydrogen Sulfide in Redox Biology Part A & B. Methods in Enzymology 2015; 554:271-97.
2. Shen X, Kolluru GK, Shuai Y, Kevil CG. Measurement of H₂S In Vivo and In Vitro by the Monobromobimane Method. Methods in Enzymology 2015; 554:31-45.

Selected Publications

1. Rajpal S, Katikaneni P, Deshotels M, Pardue S, Glawe J, Shen X, Akkus N, Modi K, Bhandari R, Dominic P, Reddy P, Kolluru GK, Kevil CG. Total sulfane sulfur bioavailability reflects ethnic and gender disparities in cardiovascular disease. Redox Biol. 2018 May;15:480-489.
2. Kolluru GK, Shen X, Yuan S, Kevil CG. Gasotransmitter Heterocellular Signaling. Antioxid Redox Signal. 2017 Jun 1;26(16):936-960.
3. Kolluru GK, Cai M, Wang K, Kevil CG, Ahmed A. Cystathionine gamma-lyase/Hydrogen sulphide (H2S) role in complications of diabetic pregnancy. DIABETIC MEDICINE 34, 38-38.
4. D'Alessandro A, Nemkov T, Sun K, Liu H, Song A, Monte AA, Subudhi AW, Lovering AT, Dvorkin D, Julian CG, Kevil CG, Kolluru GK, Shiva S, Gladwin MT, Xia Y, Hansen KC, Roach RC. AltitudeOmics: Red Blood Cell metabolic adaptation to high altitude hypoxia. J Proteome Res. 2016 Sep 20.
5. Kolluru GK, Bir SC, Yuan S, Shen X, Pardue S, Wang R, Kevil CG. Cystathionine γ-lyase regulates arteriogenesis through NO-dependent monocyte recruitment. Cardiovasc Res. 2015 Sep 1;107(4):590-600.
6. Bir SC, Pattillo CB, Pardue S, Kolluru GK, Shen X, Giordano T, Kevil CG. Nitrite anion therapy protects against chronic ischemic tissue injury in db/db diabetic mice in a NO/VEGF-dependent manner. Diabetes. 2014 Jan;63(1):270-81.
7. Kolluru GK, Shen X, Bir SC, Kevil CG. Hydrogen sulfide chemical biology: pathophysiological roles and detection. Nitric Oxide. 2013 Nov 30;35:5-20.
8. Kolluru GK, Shen X, Kevil CG.A tale of two gases: NO and H2S, foes or friends for life? Redox Biol. 2013 May 23;1(1):313-8.
9. Kolluru GK, Kevil CG. Beets, bacteria, and blood flow: a lesson of three Bs. Circulation. 2012 Oct 16;126(16):1939-40.
10. Bir SC, Kolluru GK, McCarthy P, Shen X, Pardue S, Pattillo CB, Kevil CG. Hydrogen sulfide stimulates ischemic vascular remodeling through nitric oxide synthase and nitrite reduction activity regulating hypoxia- inducible factor-1α and vascular endothelial growth factor-dependent angiogenesis. J Am Heart Assoc. 2012 Oct;1(5):e004093.
11. Kolluru GK, Bir SC, Kevil CG. Endothelial dysfunction and diabetes: effects on angiogenesis, vascular remodeling, and wound healing. Int J Vasc Med. 2012; 2012:918267.
12. Muley A, Majumder S, Kolluru GK, Parkinson S, Viola H, Hool L, Arfuso F, Ganss R, Dharmarajan AM and Chatterjee S. Secreted Frizzled-Related Protein 4: An Angiogenesis Inhibitor. Am J Pathol. 2010;176(3):1505-16

Complete List of my Published Work