First 11 pages of thesis. - OPUS - Universität Würzburg

More documents

Recommendations

Info

Interestingly, BH4 supplementation resulted in decreased atherosclerosis, decreased superoxide and increased nitric oxide in this transgenic mice. Taken together, all these studies show that the presence of a functionally active eNOS is essential for the prevention of atherosclerosis. 1.6.2 Role of nNOS in cardiovascular diseases Nitric oxide generated by nNOS functions as a non-adrenergic non- cholinergic neurotransmitter in the autonomous nervous system. Non- adrenergic non-cholinergic perivascular nerves (nitrergic nerves) found in the adventitia of cerebral and certain peripheral arteries (e.g. mesenteric, renal and femoral arteries) contain nNOS. In perivascular nitrergic nerves, nNOS derived nitric oxide causes relaxation of adjacent vascular smooth muscle cells, counterbalancing vasoconstriction mediated by the sympathetic nervous system 152 . nNOS expressed in cardiomyocytes plays an important role in regulating cardiac function 153 . In this respect, deletion of nNOS resulted in a higher heart rate and decreased heart rate variance compared to wildtype mice 154 . Genetic deficiency of nNOS resulted in increased myocardial infarction size and increased superoxide formation suggesting that nNOS serves a protective role in myocardial injury 155 . Following myocardial reperfusion injury, lack of nNOS resulted in a significant increase in cardiac polymorphonuclear leukocyte infiltration 156 . Recent studies have shown the expression of nNOS in normal vascular smooth muscle cells of carotid 157 , coronary 158 and pulmonary 159 arteries and the aorta 160 . In the absence of functional eNOS under pathophysiological conditions, nNOS may regulate normal vascular tone 160 . Further, studies have - 30 -
shown that nNOS inhibits leukocyte/endothelial cell interactions in the cremasteric microcirculation of mice, in the absence of eNOS 161 . In a mouse carotid artery ligation model, nNOS derived nitric oxide suppresses both neointimal formation and constrictive vascular remodelling 162 . In the same study the authors have shown that nNOS exerts an important inhibitory effect on vasoconstrictor response following balloon injury. Though there was no expression of nNOS before vascular injury, nNOS was up regulated in the neointima and medial smooth muscle cells after carotid artery ligation and balloon injury, suggesting a vasoprotective effect of nNOS in response to injury. Gene transfer of nNOS in venous bypass grafts resulted in substantial reduction of adhesion molecule expression and inflammatory cell infiltration in early venous bypass grafts (3 days after operation) 163 . In late venous bypass grafts (28 days after operation), nNOS gene transfer resulted in reduction of smooth muscle cell hyperplasia and reduced vascular superoxide production 163 . nNOS is detected in endothelial cells and macrophages in both early and advanced atherosclerotic lesions in humans, while it is absent in normal vessels 164 . nNOS is also expressed in the carotid artery of spontaneously hypertensive rats 157 and in the aorta of apoE ko 165 and apoE/iNOS double knockout (dko) mice 166 . Because nNOS is induced in various vascular pathologies like atherosclerosis, vascular injury and hypertension, nNOS should not be considered a “constitutive” enzyme. Rather, nNOS is subject to expressional regulation in the vascular system, while it is constitutively expressed in the nervous system 167 . We have recently shown that genetic deletion of nNOS resulted in accelerated atherosclerosis in apoE ko mice 165 , suggesting that nNOS is atheroprotective. We also showed that nNOS improves - 31 -
Page 1 and 2: Insight into oxidative stress media
Page 3 and 4: Eidesstattliche Erklärungen Hiermi
Page 6 and 7: Acknowledgements First and foremost
Page 8 and 9: “Research is to see what everybod
Page 10 and 11: Chapter 2 37 2.0 Materials and Meth
Page 12 and 13: Summary and Hypothesis 76 Zusammenf
Page 14 and 15: 1.0 Introduction Atherosclerosis, t
Page 16 and 17: which contribute to the lipid rich
Page 18 and 19: 1.2 Risk Factors Atherosclerosis ha
Page 20 and 21: 1.2.2 Environmental factors 1. High
Page 22 and 23: 1.3 Oxidative Stress Oxidative stre
Page 24 and 25: peroxynitrite 38 which by itself ca
Page 26 and 27: Pharmacological inhibition of nitri
Page 28 and 29: 1.4 The nitric oxide pathway in ath
Page 30 and 31: of NADPH, FAD and FMN, whereas the
Page 32 and 33: isoforms to the regulatory and targ
Page 34 and 35: perinuclear/golgi region within the
Page 36 and 37: nNOS interacts with several protein
Page 38 and 39: iNOS expression is regulated transc
Page 40 and 41: transport pathway and is an essenti
Page 44 and 45: the survival rate, as apoE/nNOS dko
Page 46 and 47: The seemingly opposing effects of i
Page 48 and 49: The purpose of the study presented
Page 50 and 51: 2.0 Materials and Methods 2.1 Mater
Page 52 and 53: Reagents Source For Immunohistochem
Page 54 and 55: Others Reagents Source Pegulated Su
Page 56 and 57: 2.2 Methods 2.2.1 Detection of free
Page 58 and 59: 2.2.1.2 Principle of ESR ESR spectr
Page 60 and 61: spectra 190 . Addition of exogenous
Page 62 and 63: ings were prepared as mentioned abo
Page 64 and 65: X-band EMX spectroscope (Bruker Bio
Page 66 and 67: minutes. At last sections were wash
Page 68 and 69: 3.0 Results 3.1 eNOS is a significa
Page 70 and 71: 3.2 eNOS deletion decreases vascula
Page 72 and 73: 3.3 nNOS contributes little to vasc
Page 74 and 75: 3.5 iNOS contributes significantly
Page 76 and 77: Figure 13. Determination of iNOS de
Page 78 and 79: 3.8 iNOS deletion influences NADPH
Page 80 and 81: 4.0 Discussion 4.1 eNOS is a major
Page 82 and 83: in our apoE/eNOS dko model, these a
Page 84 and 85: under conditions of substrate or co
Page 86 and 87: vessels with the iNOS specific inhi
Page 88 and 89: Summary and Hypothesis The principl
Page 90 and 91: Zusammenfassung und Hypothese Stick
Page 92 and 93:
Bibliography 1. Gimbrone MA, Jr. Va
Page 94 and 95:
xanthine oxidase contributes to vas
Page 96 and 97:
expression of adhesion molecules an
Page 98 and 99:
transforming growth factor-beta 1.
Page 100 and 101:
generation from neuronal nitric oxi
Page 102 and 103:
148. Lee PC, Wang ZL, Qian S, Watki
Page 104 and 105:
174. Mayr U, Zou Y, Zhang Z, Dietri
Page 106 and 107:
implications in intracellular fluor
Page 108 and 109:
Definitions Thesaurus • Allograft
Page 110 and 111:
• Claudication refers to leg pain
Page 112 and 113:
cases per year in the US. It is a n
Page 114 and 115:
Curriculum Curriculum vitae vitae N
Page 116 and 117:
presentation at the 37 th Annual co
show all

First 11 pages of thesis. - OPUS - Universität Würzburg

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?