UTMB Department of Pathology

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Mechanisms of Toxic Injury in the Blood Vessel Wall

In my laboratory, I am interested in how the larger blood vessels of the body are injured by toxic chemicals in our environment. The area of greatest concentration for this work is the muscular wall of these blood vessels, or the "media." Experimental drugs and other chemicals that protect against such injury–or predispose to injury –are under investigation in the hope that someday we may be able to manipulate the blood vessel wall to delay the commonest degenerative diseases that result in great human morbiditiy and mortality, including atherosclerosis and aneurysm.

Specifically, my laboratory has been defining the cellular and biochemical events that occur during vascular injury by toxic chemicals that are relevant to the environment, or to cigarette smoke components. Past emphasis has been on the metabolism of vasculotoxic amines to aldehydes, but recent work has defined how glutathione-S-transferases act in the defense of vascular wall against reactive molecules both in vivo and in vitro. Important contributions to the understanding of the role played by coronary arterial vasospasm in myocardial injury have been made by Dr. Daniel Conklin, resulting in several seminal papers in toxicology and vascular journals. The role of these defense mechanisms during cellular injury of the vascular wall by atherosclerosis has also been recently examined in our lab. New directions have been undertaken into the area of "developmental vasculotoxicity" originally started by a graduate of the lab, Dr. Shannon Langford.

Perhaps the most exciting new direction of the laboratory has been our very recent development of a model of dissecting aortic aneurysm. Our initial studies into this small animal model have revealed several pathways of fibrillogeneisis of collagen and elastin that may prove to be targets of toxic insult early in life, or even during embryologic development, resulting in this deadly disease which is just now coming to be recognized as a common killer of young persons. Hence, our studies delve into the most basic phenomena underlying aging, aneurysm formation, and the atherosclerotic process.

1. Conklin, DJ, Cowley, HR, Wiechmann, RJ, Johnson, GH, Trent, MB, Boor PJ. Vasoactive Effects of Methylamine in Isolated Human Blood Vessels: Role of Semicarbazide-Sensitive Amine Oxidase, Formaldehyde, and Hydrogen Peroxide. Am. J. Physiol. Heart Circ. Physiol. 286:H667-676, 2004
2. Yang, Y, Yang, Y, Trent, MB, He, N, Lick, SD, Zimniak, P, Awasthi, YC. Boor, PJ. Glutathione-S-Transferase A4-4 Modulates Oxidative Stress in Endothelium: Possible Role in Human Atherosclerosis. Atherosclerosis 173:211-221, 2004
3. Dugas, TR, Kanz, MF, Hebert, VY, Hennard, KL, Liu, H., Santa Cruz, V, Conklin, D, Boor, PJ. Vascular Medial Hyperplasia Following Chronic, Intermittent Exposure to 4,4’-Methylenedianiline. Cardiovas. Tox. 4:85-96, 2004
4. Khan MF, Wu X, Boor PJ, Ansari GAS. Nitrotyrosine formation in splenic toxicity of aniline. Toxicology 194: 95-102, 2003
5. Sharma, R, Yang, Y, Sharma, A, Dwivedi, S, Popov, VL, Boor PJ, Singhal, SS, Awasthi S, Awasthi YC. Mechanisms and Physiological Significance of the Transport of 4-Hydroxynonenal-Glutathione Conjugate in Human Lens Epithelial Cells. Invest Ophthal Visual Sci 44:3438-3449, 2003
6. Khan MF, Wu X, Ansari GAS, Boor PJ. Malondialdehyde-protein adducts in the spleens of aniline-treated rats: Immunohistochemical detection and localization. J Toxicol Environ Health, Part A 66: 93-102, 2003
7. Langford, SD, Trent, MB, Boor, PJ. Semicarbazide-Sensitive Amine Oxidase and Extracellular Matrix Deposition by Smooth-Muscle Cells. Cardiovas Toxicol. 2:141-150, 2002
8. Khan, MF, Wu, X., Tipnis, UR, Ansari, GAS, Boor PJ, Protein adducts of malondialdehyde And 4-hydroxynonenal in livers of iron-loaded rats: quantitation and localization. Toxicology 173: 193-201, 2002
9. Trent, MB, Conklin, DJ, Boor, PJ. Culture Medium Enhances Semicarbazide-Sensitive Amine Oxidase Activity. In Vitro Cell. Dev. Biol-Animal 38:523-528, 2002
10. Conklin DJ, Boyce, CL, Trent, MB, Boor, PJ. Amine metabolism: a novel path to coronary artery vasospasm. Toxicol. Appl. Pharmacol 175: 149-159, 2001
11. Slukvin, II, Boor, P, and Jerrells, TR. Initiation of alcoholic fatty liver and hepatic inflammation with a specific recall immune response in alcohol-consuming C57BI/6 mice. Clin Exp Immunol. 125: 123-133, 2001
12. Srivastava, S., Conklin, D.J., Boor, PJ, Liu, S.Q., Srivastava, S.K., and Bhatnagar, A. Identification of biochemical pathways for the metabolism of oxidized low-density lipoprotein-derived aldehyde, 4-hydroxy trans-2-nonenal, in vascular smooth muscle cells. Atherosclerosis 158: 339-350, 2001
13. Langford, SD, Trent MB, Boor PJ, Cultured rat vascular smooth muscle cells are resistant to methylamine toxicity: No correlation to semicarbazide-sensitive amine oxidase. Cardiovasc. Toxicol 1: 51-60, 2001
14. Otero, FJ, Boor, PJ, and Sheahan, RG. Doxorubicin Induced Cardiomyopathy. A. J. Med. Sci. 320 (1): 59-68, 2000
15. Tipnis, UR, He, G-Y, Li, S, Campbell, G, Boor, PJ. Attenuation of isoproterenol-meditated myocardial injury in rat by an inhibitor of polyamine synthesis. Cardiovasc. Pathol. 9:273-280, 2000
16. Vertrees, RA, Zwischenberge,r JB, Boor, PJ, Pencil, SD. Oncogenic ras results in increased cell kill due to defective thermoprotection in lung cancer cells. Ann. Thoracic Surg. 69: 1675-1780, 2000
17. Vertrees, RA, Deyo, DJ, Quast, M, Wei, G, Lightfoot, KM, Boor, PJ, Zwischenberger, JB. Development of human to murine orthotopic xenotransplanted lung cancer model. J. Invest. Surg. 13: 1-10, 2000
18. Ware, DL, Boo,r P, Yang C, Gowda A, Motamedi M. Ventricular arrhythmias following thermal damage of epicardial tissue: Possible causes and clinical implications. Pacing and Cardiac Electrophysiology 23: 1375-1380, 2000
19. Khan, MF, Wu, X, Boor, PJ, and Ansari, GAS. Oxidative Modification of Lipids and Proteins in Aniline-Induced Splenic Toxicity. Toxicol. Sci. 48:134-140, 1999
20. Khan, MF, Wu, X, Alcock, NW, and Boor, PJ. Iron exacerbates aniline-associated splenic toxicity. J. Toxicol. Environ. Hlth. Part A, 57:101-112, 1999
21. Langford, SD, Trent, MB, Balakumaran, A, and Boor, PJ. Developmental Vasculotoxicity Associated with Inhibition of Semicarbazide-Sensitive Amine Oxidase. Toxicol. Appl. Pharmacol. 155:237-244, 1999
22. Conklin, DJ, Trent MB, and Boor PJ. The role of plasma semicarbazide-sensitive amine oxidase in allylamine and -aminopropionitrile cardiovascular toxicity: mechanisms of myocardial protection and aortic media injury in rats. Toxicology 138:137-154, 1999
23. He N, Singhal SS, Awasthi S, Zhao T and Boor PJ. Role of Glutathione S-transferase 8-8 in Allylamine Resistance of Vascular Smooth Muscle Cells in Vitro. Toxicol. Appl. Pharmacol. 158:177-185, 1999
24. Ware, DL, Boor, PJ, Yang C, Gowda, A, Motamedi, M. Slow Intramural Heating with Diffused Laser Light: A Novel Method for Ablation of Post-Infarction Ventricular Tachycardia. Circulation 99:1630-1636, 1999
25. Kumar D, Trent MB and Boor PJ. Allylamine & -Aminopropionitrile Induced Aortic Medial Necrosis: Mechanisms of Synergism. Toxicology 125:107-115, 1998
26. Khan MF, Green SM, Ansari, GAS and Boor PJ. Phenylhydroxylamine: Role in Aniline-Associated Splenic Oxidative Stress and Induction of Subendocardial Necrosis. Toxicol. Sci. 42:64-71, 1998
27. Conklin DJ and Boor PJ. Allylamine Cardiovascular Toxicology: Evidence for Aberrant Vasoreactivity in Rats. Toxicol. App. Pharmacol. 148:245-251, 1998
28. Conklin, DJ, Langford, SD, and Boor, PJ. Contribution of Serum and Cellular Semicarbazide-Sensitive Amine Oxidaxe to Amine Metabolism and Cardiovascular Toxicity. Toxicol. Sci. 46:386-392, 1998
29. Lick SD, Sankar AB and Boor, PJ. Heart Donation After Lightning Strike. J. Heart Lung Transplant. 17:1034-1035, 1998.
30. He, NG, Awasthi, S, Singhal, SS,Trent, MB, and Boor, PJ. The role of glutathione S-transferases as a defense against reactive electrophiles in the blood vessel wall. Toxicol. Appl. Pharmacol. 152:83-89, 1998
31. Khan MF, Wu X, Kaphalia BS, Boor PJ and Ansari, GAS. Acute hematopoietic toxicity of aniline in rats. Toxicol. Lett. 92:31-37, 1997
32. Khan MF, Boor PJ, Gu Y, Alcock NW and Ansari GAS. Oxidative stress in the splenotoxicity of aniline. Fundam. Appl. Toxicol. 35:22-30, 1997
33. Awasthi S and Boor PJ. Allylamine and -aminopropionitrile-induced vascular injury: Enhanced expression of high-molecular-weight proteins. J. Toxicol. and Environ. Health. 52:101-116, 1997
34. Adegboyega P, Adesokan A, Haque A and Boor PJ. Sensitivity and specificity of triphenyl tetrazolium chloride in the gross diagnosis of acute myocardial infarcts. Arch. Pathol. Lab. Med. 121:1063-1068, 1997
35. Amrikachi M, Lopez L, Cutler D and Boor, PJ. Lactobacillus endocarditis: a chronic active infection. Cardiov. Path. 6:341-344, 1997
36. Adegboyega PA, Haque AK, and Boor PJ. Extensive myocytolysis as a marker of sudden cardiac death. Cardiovasc. Pathol. 5:315-321, 1996
37. Langford SD, Boor PJ. Oleander Toxicity: An examination of human and animal toxic exposures. Toxicology 109: 1-13, 1996
38. Boor PJ, Gotlieb AI, Joseph EC, Kerns WD, Roth RA, Tomaszewski KE. Contemporary Issues in Toxicology: Chemical-Induced Vasculature Injury. Toxicol. Appl. Pharmacol. 132:177-195, 1995
39. Khan MF, Boor PJ, Kaphalia BS, Alcock NW, Ansari, GAS. Hematopoietic toxicity of linoleic acid anilide: Importance of Aniline. Fund. Appl. Toxicol. 25(2): 224-232, 1995
40. Misra P, Srivastava SK, Singhal SS, Awasthi S, Awasthi YC, Boor PJ. Glutathione-S-Transferase (GST) 8-8 is localized in smooth muscle cells of rat aorta and is induced in an experimental model of atherosclerosis. Toxicol. Appl. Pharmacol. 133: 27-33, 1995
41. Awasthi S, Boor, PJ. Lipid peroxidation and oxidative stress during acute allylamine-induced cardiovascular toxicity. J. Vasc. Res. 31:33-41, 1994
42. Trent MB, Boor PJ. Vascular amine oxidase activities during synergistic vasculotoxicity. Toxicology 89: 67-77, 1994
43. Tipnis UR, Haile C, Boor PJ, Gutkowska J. Polyamine regulation of atrial natriuretic peptide in cultured cardiocytes. Reg. Peptides 52: 75-84, 1994
44. Awasthi S, Boor PJ. Semicarbazide protection from in vivo oxidant injury of vascular tissue by allylamine. Tox. Letters 66: 157-163, 1993
45. Khan MF, Kaphalia BS, Boor PJ, Ansari GAS. Subchronic toxicity of aniline hydrochloride in rats. Arch Environ. Contam. Toxicol. 24:368-374, 1993
46. Kaphalia BS, Khan MF, Boor PJ, Ansari GAS. Toxic response to repeated oral administration of 2-chloroethyl linoleate in rats. Res. Commun. Chem. Path. Pharmacol. 76:209-222, 1992
47. Tipnis UR, Boor PJ. Inhibition of polyamine synthesis impairs the secretion of atrial natriuretic peptide. Regulatory Peptides, 37: 227-236, 1992
48. Tipnis UR, Tao M, Boor PJ. Purification and characterization of semicarbazide-sensitive amine oxidase from porcine aorta. Cell Mol Biology 38: 575-584, 1992
49. Boor PJ, Trent MB, Lyles GA, Tao M, Ansari, GAS. Methylamine metabolism to formaldehyde by a vascular enzyme. Toxicology, 73: 251-258, 1992
50. Sklar JL, Anderson PG, Boor PJ. Allylamine and acrolein toxicity in perfused rat hearts. Toxicol Appl Pharmacol 107: 535-544, 1991
51. Anderson PG, Digerness SB, Sklar JL, Boor PJ. Use of the isolated perfused heart for evaluation of cardiac toxicity. Toxicol Pathol 18: 497-510, 1991
52. Boor PJ, Khan MF, Kaphalia BS, Jerrells TR, Ansari GAS. Synergistic vascular toxicity and fatty acid anilides in the Toxic Oil Syndrome. J. Am. Coll. Cardiol. 18:1824-1828, 1991
53. Kumar D, Hysmith RM, Boor PJ. Allylamine and  aminopropionitrile induced vascular injury: an in vivo and in vitro study. Toxicol Appl Pharmacol 103: 288-302, 1990
54. Boor PJ, Hysmith RM, Sanduja R. A role for a new vascular enzyme in the metabolism of xenobiotic amines. Circ. Res. 66:249-252, 1990
55. Boor PJ, Kretschmer, N. Increased DNA synthesis in the heart during acute allylamine cardiotoxicity. Res. Comm. Chem. Pathol. Pharmacol. 68:3-11, 1990
56. Arnold JR, Hysmith RM, Boor PJ. The ultracytochemical demonstration of extramitochondrial monoamine oxidase activity. Biogenic Amines 7: 127-143, 1990.
57. Sanduja R, Ansari GAS, Boor PJ. 3-Hydroxypropylmercapturic acid: A biologic marker of exposure to allylic and related compounds. J Appl Toxicol 9(4): 235-238, 1989
58. Rutledge JM, Boor PJ. Eisenmenger's: A case study and review of the syndrome and complex. Am J Cardiovasc Pathol 2: 285-294, 1989
59. Hysmith RM, Boor PJ. Role of benzylamine oxidase in the cytotoxicity of allylamine toward aortic smooth muscle cells. Toxicology 51: 133-145, 1988
60. Hysmith RM, Boor PJ. Purification of cellular and extracellular benzylamine oxidase from cultured porcine aortic smooth muscle cells. Biochem Cell Biol 66: 821-829, 1988
61. Stout LC, Boor PJ, Horton E. Myofibroblastic proliferation on mitral valve chordae tendineae. A distinctive lesion associated with alcoholic liver disease. Human Pathology 19: 720-725, 1988
62. Ahmed AE, Grissom M, el-Azhary R, Haque A, Boor PJ, Costanzi J. Studies on the mechanism of CCNU-induced hepatotoxicity II: Biochemical and morphological characterization of the injury and its prevention by phenobarbital. Canc. Chemother. Pharmacol. 19: 103-108, 1987.
63. Hysmith RM, Boor PJ. Binding of [14C] allylamine to isolated mitochondria and rat heart and aorta. Toxicology 44: 13-29, 1987
64. Hysmith RM, Welch TK, Boor PJ. The comparative study of cardiovascular toxins utilizing a sensitive indicator of sublethal toxic injury. In Vitro Cell Devel. Biol. 23:129-133, 1987
65. Hysmith RM, Boor PJ. In vitro expression of benzylamine oxidase activity in cultured porcine aortic smooth muscle cells J Cardiovasc Pharmacol 9:668-674, 1987
66. Boor PJ, Hysmith RM. Allylamine cardiovascular toxicity: A Review. Toxicology 44:129-144, 1987
67. Kretschmer NW, Boor PJ, el-Azhary R, Ahmed AE, Reynolds ES. Studies on the mechanism of CCNU hepatotoxicity III: Ultra-structural study of bile ducts. Canc. Chemother Pharmacol 19: 109-117, 1987
68. Sanduja R, Ansari GAS, Boor PJ. Simultaneous determination of myocardial creatine phosphate and adenine nucleotides by reverse phase high performance liquid chromatography. Biomed Chromatogr 2: 156-158, 1987
69. Boor PJ, Sanduja R, Nelson TJ, Ansari GAS. In vivo metabolism of the cardiovascular toxin, allylamine. Biochem. Pharmacol. 36:4347-4353, 1987
70. Ansari GAS, Kaphalia B, Boor PJ. Selective pancreatic toxicity of palmitoylpentachlorophenol. Toxicology 46: 57-63, 1987
71. Hysmith RM, Boor PJ. Comparative toxicity of the cardiovascular toxin allylamine to porcine aortic smooth muscle and endothelial cells. Toxicology 38: 141-150, 1986
72. Boor PJ, Ansari GAS. A high performance liquid chromatographic method for quantitation of acrolein in biological samples. J. Chromatogr. Biomed. Appl. 375:159-164, 1986
73. Arnold JR, Boor PJ. A new method of processing cultured cells for transmission electronmicroscopy: The floating sheet. J Tissue Cult Methods 10(4): 223-226, 1986
74. Arnold JR, Boor PJ. Improved transmission electronmicroscopy (TEM) of cultured cells through a "floating sheet" method. J. Ultrastr. Molec. Struct. Res. 24:30-36, 1986
75. Douidar S, Boor PJ, Ahmed AE. Potentiation of hepatotoxic effect of acetaminophen by prior administration of salicylate. J. Pharmacol. Exp. Ther. 233:242-248, 1985
76. Ghanayem BI, Boor PJ, Ahmed AE. Gastric glutathione depletion mediates acrylonitrile induced gastric ulceration. J. Pharmacol. Exp. Ther. 232:570-577, 1985
77. Boor PJ. Allylamine cardiovascular toxicity V: Tissue distribution and toxicokinetics after oral administration. Toxicology 35: 167-177, 1985
78. Boor PJ, Ferrans VJ. Ultrastructural alterations in allylamine cardiovascular toxicity: late myocardial and vascular lesions. Am J Pathol 121: 39-54, 1985
79. Hysmith RM, Boor PJ. Allylamine vascular toxicity VI: Subcellular distribution in rat aorta. Toxicology 35: 179-187, 1985
80. Chieco P, Boor PJ. Quantitative histochemistry in pathology and toxicology: An evaluation of the original two wavelength method of Ornstein. Lab Invest 50: 355-362, 1984
81. Ghanayem BI, Ahmed AE, Boor PJ. Acetyl salicylic acid induced gastric mucosal lesions: no role of gastric glutathione. Res. Comm. Chem. Pathol. Pharmacol. 45:153-156, 1984
82. Chieco P, Normanni P, Boor PJ. Improvement in soluble dehydrogenase histochemistry by nitroblue tetrazolium uptake before incubation: A qualitative and quantitative study. Stain Technol. 59: 201-211, 1984
83. Aversano R, Boor PJ. Histochemical alterations in acute and chronic doxorubicin cardiotoxicity. J. Molec. Cell. Cardiol. 15: 543-553, 1983
84. Aversano R, Boor PJ. Acute doxorubicin induced cardiac arrhythmias during ether anesthesia. Res. Comm. Chem. Pathol. Pharmacol. 41: 345-348, 1983
85. Chieco P, Boor PJ. Use of low temperatures for glutathione histochemical stain. J. Histochem. Cytochem. 31:975-976, 1983
86. Boor PJ, Ferrans VJ. Ultrastructural alterations in allylamine induced cardiomyopathy: Early lesions. Lab Invest 47: 76-86, 1982
87. Nelson TJ, Boor PJ. Allylamine cardiotoxicity: IV. Metabolism to acrolein by cardiovascular tissue. Biochem. Pharmacol. 31: 509-514, 1982
88. Boor PJ, Nelson TJ. Biotransformation of the cardiovascular toxin, allylamine, by rat and human cardiovascular tissue. J. Molec. Cell. Cardiol. 14:679-682, 1982
89. Van Ding T, Boor PJ, Garza JR. Massive pulmonary embolism following delivery in a patient with sickle cell trait. Amer. J. Ob. Gyn. 143:722-724, 1982
90. Boor PJ. Studies of hypotension and cardiac flow in isoproterenol induced myocardial necrosis. Exptl. Molec. Pathol. 34:110-121, 1981
91. Evans AT, Korndorffer WE, Boor PJ. Sudden death of two brothers while playing basketball: Familial hypertrophic cardiomyopathy. Texas Med. 76(9): 48-51, 1980
92. Boor PJ, Nelson TJ, Chieco P. Allylamine cardiotoxicity: II. Histopathology and histochemistry. Am J Pathol 100: 739-764, 1980
93. Boor PJ, Nelson TJ. Allylamine cardiotoxicity: III. Protection by semicarbazide and in vivo derangement of monoamine oxidase. Toxicology 18: 87-102, 1980
94. Reynolds ES, Moslen MT, Boor PJ, Jaeger RT. 1,1-Dichloro-ethylene hepatotoxicity: Time course of glutathione changes and biochemical aberrations. Am J Pathol 101:331-344, 1980
95. Boor PJ, McAllister PR. Juxtaposition of the atrial appendages. Human Pathol 10(3):347-349, 1979
96. Boor PJ, Swanson MR. Papillary cystic neoplasm of the pancreas. Am. J. Surg. Pathol. 3(1): 69-75, 1979.
97. Boor PJ. Cardiac glutathione: Diurnal rhythm and variation in drug induced cardiomyopathy. Res. Comm. Chem. Pathol. Pharmacol. 24(1) :27-36, 1979.
98. Boor PJ, Moslen MT, Reynolds ES. Allylamine cardiotoxicity: I. Sequence of pathologic events. Toxicol Appl Pharmacol 50: 581-592, 1979.
99. Boor PJ, Ferrans VJ, Jones M, Kawanami 0, Thiedemann KU, Herman EH, Roberts WC. Tubuloreticular structures in myocardium, an ultrastructural study. J. Molec. Cell. Cardiol. 11: 967-979, 1979
100. Boor PJ, Reynolds ES. Myocardial infarct size: Clinicopathologic agreement and discordance. Human Pathol 8(6): 685-695, 1977
101. Boor PJ, Reynolds ES. A simple planimetric method for determination of left ventricular and necrotic myocardial mass. Am. J. Clin. Pathol 68(3): 389-392, 1977
102. Moslen MT, Reynolds ES, Boor PJ, Bailey K, Szabo S. Trichloroethylene induced deactivation of cytochrome P450 and loss of liver glutathione in vivo. Res. Comm. Chem. Pathol. Pharmacol. 16(1): 109-120, 1977
103. Szabo S, Bailey KA, Boor PJ, Jaeger RJ. Acrylonitrile and tissue glutathione: Differential effect of acute and chronic interactions. Biochem. Biophys. Res. Comm. 79(1): 32-37, 1977
104. Boor PJ, Reynolds ES, Moslen MT. Neurotoxicity of digitoxin in adult and newborn rats: Drug distribution. Arch. Inter. Pharm. Ther. 224(1): 4-12, 1976
105. Boor PJ, Schoene WC. Fetal cerebellar tissue associated with a primitive neuroepithelial tumor in ovarian teratoma. The Canadian Journal of Neurological Sciences 2: 139-140, 1975
106. Tilney NL, Boor PJ. Host response to implanted dacron grafts. Arch. Surg. 10:1469-1472, 1975

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