Mark T. Quinn

Bio: Mark T. Quinn is an academic researcher from Montana State University. The author has contributed to research in topics: NADPH oxidase & Superoxide. The author has an hindex of 77, co-authored 251 publications receiving 23204 citations. Previous affiliations of Mark T. Quinn include University of California, San Diego & Scripps Research Institute.

Oxidatively modified low density lipoproteins: a potential role in recruitment and retention of monocyte/macrophages during atherogenesis

Abstract: Previous studies in this laboratory established that low density lipoprotein (LDL) incubated with cultured endothelial cells, smooth muscle cells, or macrophages undergoes free radical-catalyzed oxidative modification that generates lipid peroxides and extensive structural changes in the LDL molecule. The oxidatively modified LDL strongly inhibited chemotactic responses of the mouse resident peritoneal macrophage. The present studies show that this oxidized LDL does not inhibit the motility of mouse monocytes and actually exhibits a chemotactic activity for human monocytes; the chemotactic activity of the oxidized LDL resides in the lipid fraction. These findings allow us to propose a pathogenetic sequence by which elevated plasma LDL levels, followed by oxidative modification in the arterial wall, could sufficiently account for the generation of the lipid-laden foam cells and the initiation of the fatty streak, the earliest well-defined lesion in atherogenesis.

Superoxide Production and Expression of Nox Family Proteins in Human Atherosclerosis

Abstract: Background— NAD(P)H oxidases are important sources of superoxide in the vasculature, the activity of which is associated with risk factors for human atherosclerosis. This study was designed to investigate the localization of superoxide production and the expression of the Nox family of NAD(P)H oxidase proteins (gp91phox, Nox1, and Nox4) in nonatherosclerotic and atherosclerotic human coronary arteries. Methods and Results— In coronary artery segments from explanted human hearts, we examined intracellular superoxide production with dihydroethidium. In nonatherosclerotic coronary arteries, superoxide was present homogenously throughout the intima, media, and adventitia. In atherosclerotic arteries, there was an additional intense area of superoxide in the plaque shoulder, which is rich in macrophages and α-actin–positive cells. p22phox colocalized with gp91phox mainly in macrophages, whereas Nox4 was found only in nonphagocytic vascular cells. Expression of gp91phox and p22phox mRNA was associated with the ...

Lysophosphatidylcholine: a chemotactic factor for human monocytes and its potential role in atherogenesis

Abstract: Native low density lipoprotein (LDL) does not affect monocyte/macrophage motility. On the other hand, oxidatively modified LDL inhibits the motility of resident peritoneal macrophages yet acts as a chemotactic factor for circulating human monocytes. We now show that lysophosphatidylcholine (lyso-PtdCho), which is generated by a phospholipase A2 activity during LDL oxidation, is a potent chemotactic factor for monocytes. It is not chemotactic for neutrophils or for resident macrophages. Platelet-activating factor, after treatment with phospholipase A2, becomes chemotactic for monocytes, whereas the intact factor is not. Synthetic 1-palmitoyl-lyso-PtdCho showed chemotactic activity comparable to that of the lyso-PtdCho fraction derived from oxidized LDL. The results suggest that lyso-PtdCho in oxidized LDL may favor recruitment of monocytes into the arterial wall during the early stages of atherogenesis. Generation of lyso-PtdCho, either from LDL itself or from membrane phospholipids of damaged cells, could play a more general role in inflammatory processes throughout the body.

Novel Competitive Inhibitor of NAD(P)H Oxidase Assembly Attenuates Vascular O2− and Systolic Blood Pressure in Mice

Abstract: We previously reported enhanced expression of the p67 phox and gp91 phox components of NAD(P)H oxidase in angiotensin (Ang) II–induced hypertension, suggesting de novo assembly in response to Ang II. To examine the direct involvement of NAD(P)H oxidases in Ang II–induced O 2 − production, we designed a chimeric peptide that inhibits p47 phox association with gp91 phox in NAD(P)H oxidase (gp91ds- tat ). This was achieved by linking a 9-amino acid peptide (aa) derived from HIV-coat protein ( tat ) to a 9-aa sequence of gp91 phox (known to interact with p47 phox ). As a control, we constructed a chimera containing tat and a scrambled gp91 sequence (scramb- tat ). We found that gp91ds- tat decreased O 2 − levels in aortic rings treated with Ang II (10 pmol/L) but had no effect on either the O 2 − -generating enzyme xanthine oxidase or potassium superoxide–generated O 2 − . We infused vehicle, Ang II (0.75 mg · kg −1 · d −1 ), Ang II+gp91ds- tat (10 mg · kg −1 · d −1 ), or Ang II+scramb- tat intraperitoneally in C57Bl/6 mice and measured systolic blood pressure (SBP) on days 0, 3, 5, and 7 of infusion. SBP increased by day 3 in mice given Ang II and Ang II+scramb- tat but was significantly lower with Ang II+gp91- tat . On day 7, SBP was still significantly inhibited in mice given Ang II+gp91ds- tat , whereas Ang II–induced O 2 − production was inhibited throughout the aorta as detected by dihydroethidium staining, consistent with the ability of this inhibitor to block the various vascular NAD(P)H oxidase isoforms. These data support the hypothesis that inhibition of the interaction of p47 phox and gp91 phox (or its homologues) can block O 2 − production and attenuate blood pressure elevation in mice.

Atherosclerosis — An Inflammatory Disease

Abstract: Atherosclerosis is an inflammatory disease. Because high plasma concentrations of cholesterol, in particular those of low-density lipoprotein (LDL) cholesterol, are one of the principal risk factors for atherosclerosis,1 the process of atherogenesis has been considered by many to consist largely of the accumulation of lipids within the artery wall; however, it is much more than that. Despite changes in lifestyle and the use of new pharmacologic approaches to lower plasma cholesterol concentrations,2,3 cardiovascular disease continues to be the principal cause of death in the United States, Europe, and much of Asia.4,5 In fact, the lesions of atherosclerosis represent . . .

The pathogenesis of atherosclerosis: a perspective for the 1990s

Abstract: Atherosclerosis, the principal cause of heart attack, stroke and gangrene of the extremities, is responsible for 50% of all mortality in the USA, Europe and Japan. The lesions result from an excessive, inflammatory-fibroproliferative response to various forms of insult to the endothelium and smooth muscle of the artery wall. A large number of growth factors, cytokines and vasoregulatory molecules participate in this process. Our ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation.

Biochemistry and molecular cell biology of diabetic complications

Abstract: Diabetes-specific microvascular disease is a leading cause of blindness, renal failure and nerve damage, and diabetes-accelerated atherosclerosis leads to increased risk of myocardial infarction, stroke and limb amputation. Four main molecular mechanisms have been implicated in glucose-mediated vascular damage. All seem to reflect a single hyperglycaemia-induced process of overproduction of superoxide by the mitochondrial electron-transport chain. This integrating paradigm provides a new conceptual framework for future research and drug discovery.