Jorge H. Capdevila

Jorge H. Capdevila (October 6, 1940) is an American Biochemist and Professor Emeritus of Medicine at Vanderbilt University Medical School, Nashville TN. He was named Fellow of the American Heart Association in 2002 and received the 2004 American Heart Association prestigious Novartis Award for his contributions to our understanding of the molecular basis of hypertension. Dr. Capdevila’s pioneering identification of roles for the Cytochrome P450 (P450) enzymes in the metabolism of arachidonic acid (AA) and of the physiological and pathophysiological importance of these enzymes and products were recognized in an special section honoring him at the 14th International Winter Eicosanoid Conference, Baltimore MD, March 11-14, 2012. In 2017 Dr. Capdevila received an Outstanding Achievement Award from the Eicosanoid Research Foundation for his contributions to the establishment of the AA Monooxygenase as a physiological/pathophysiological important metabolic pathway. Professor Capdevila is listed as a noteworthy medical and biochemical educator in the 2008 62nd volume of Marquis “Who’s Who in America”. 
==Early life and career==
Dr. Capdevila was born in Santiago, Chile. Married Maria Antonieta Maturana, sons Cristian and Andres. He earned a degree in Biochemistry in 1969 from the University of Chile, Santiago, Chile and a Ph.D. from the University of Georgia, Athens, GA in 1975. He did postdoctoral work with Professors Sten Orrenius at the Karolinska Institutet, Stockholm, Sweden, and Russell A. Prough and Ronald W. Estabrook at the University of Texas Health Science Center at Dallas, TX [now University of Texas Southwestern (UTSW) Medical Center]. Dr. Capdevila initiated his independent research career in 1984 as a Research Assistant Professor of Biochemistry at the UTSW Medical Center, Dallas, TX, joined the faculty at the Vanderbilt University Medical School, Nashville TN in 1986 as Associate Professor of Medicine and Biochemistry, was promoted to Professor in 1991, and retired as Emeritus Professor of Medicine in 2015. Dr. Capdevila has authored 206 peer-reviewed publications and was awarded 5 US patents.
==Scientific Contributions==
The Cytochrome P450 Arachidonic Acid Monooxygenase Metabolic Pathway: Soon after his initial report of a role for the microsomal P450 enzymes in AA oxidation, Dr. Capdevila and collaborators begun studies of the biochemical and enzymatic properties of this novel metabolic pathway5 that resulted in the: a) structural characterization of 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (EETs) and 19- and 20-hydroxyeicosatetraenoic acids (19- and 20-HETEs) as products of the Epoxygenase and ω/ω-1 Hydroxylase branches of the P450 AA Monooxygenase, respectively, b) identification of the presence of pools of EETs in human and rodent organs and the establishment of the AA Epoxygenase as an endogenous metabolic pathway, c) documentation of a role for the P450 CYP2 gene subfamily in endogenous EET biosynthesis, d) identification of the presence in human and rodent urine of the EET hydration products, the vic-dihydroxyeicosatrienoic acids (DHETs), and of soluble epoxide hydrolase (sEH) as the enzyme responsible for their formation, and e) demonstration that in most organ tissues the EETs are present esterified into cellular glycerophospholipids. 
Characterization of Functional Roles for the Arachidonic Acid Epoxygenase Metabolites: Early studies by Dr. Capdevila and collaborators showed that EETs stimulated the release of brain, pituitary, and pancreatic hormones[5],[9],[10], mediated signaling by epidermal growth factor, inhibited renal Na+ and K+ transport[5], and possessed vasodilator properties. These were the first reports of EET-associated biological activities and as such, they served as an incentive for subsequent functional studies of the AA Epoxygenase and its metabolites in the USA and abroad. 
Physiological/Pathophysiological Roles of the Arachidonic Acid Monooxygenase Pathway: Capdevila’s group provided the first unequivocal evidence that members of the P450 murine Cyp4a and Cyp2c gene subfamilies participated in the control of systemic blood pressures by showing that lack of a functional: a) Cyp4a14 gene caused male specific hypertension associated with increases in the renal expression of the Cyp4a12 AA ω-Hydroxylase and the biosynthesis of the vasoconstrictor 20-HETE. The biomedical relevance of these studies was indicated by the identification of associations between variants in the human CYP4A11 gene (coding for a functional homologue of the murine Cyp4a12 20-HETE synthase) and hypertension in Caucasians and with hypertension and the progression of kidney disease in African-Americans; b) Cyp4a10 gene down-regulated the kidney expression of the Cyp2c44 AA Epoxygenase, leading to reductions in renal EET biosynthesis and dietary salt sensitive hypertension, and c) Cyp2c44 gene reduced the kidney biosynthesis and the in vivo levels of 11,12-EET and caused dietary salt sensitive hypertension associated with a hyperactive kidney epithelial sodium channel (ENaC) and increases in sodium reabsorption in the distal nephron[5]. These molecular genetics studies identified: a) 20-HETE as a renal vasoconstrictor and pro-hypertensive lipid[5],[18],[19], and b) 11,12-EET as a regulator of ENaC gating, and as an endogenous natriuretic and anti-hypertensive mediator[5],[18],[23]. Additionally, they demonstrated that salt sensitive hypertension, a prevalent form of the human disease, could result from a down-regulation or a lack of a functional Cyp2c44 AA Epoxygenase[5],[18] and suggested similar physiological/pathophysiological roles for its human catalytic homologue, CYP2C8. 
More recently Dr. Capdevila participated in the elucidation of roles for the Cyp2c44 AA Epoxygenase in tumor vascularization and progression in a rodent model of human non-small-cell-lung cancer (NSCLC), as well as in studies showing improved survival in female cases of NSCLC in carriers of two known reduction of function variants of the human CYP2C9 AA Epoxygenase gene. 
In summary, Dr. Capdevila and collaborators contributed to the identification of the biological significance of the P450 Arachidonic Acid Monooxygenase, its establishment as the third branch of the Eicosanoid Cascade, and to its current status as a physiological/pathophysiological important metabolic pathway[5]. 
Category:1940 births
Category:People from Santiago, Chile
Category:University of Chile alumni
Category:University of Georgia alumni
Category:American people
Category:American biochemists
Category:Professors