Author
Marek Bodzioch
Other affiliations: Boston Children's Hospital, University of Regensburg
Bio: Marek Bodzioch is an academic researcher from Jagiellonian University. The author has contributed to research in topics: Gene & ABCA1. The author has an hindex of 13, co-authored 18 publications receiving 2006 citations. Previous affiliations of Marek Bodzioch include Boston Children's Hospital & University of Regensburg.
Papers
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TL;DR: Evidence is presented that TD is caused by mutations in ABC1, encoding a member of the ATP-binding cassette (ABC) transporter family, located on chromosome 9q22–31, which has implications for the understanding of cellular HDL metabolism and reverse cholesterol transport, and its association with premature cardiovascular disease.
Abstract: Tangier disease (TD) is an autosomal recessive disorder of lipid metabolism. It is characterized by absence of plasma high-density lipoprotein (HDL) and deposition of cholesteryl esters in the reticulo-endothelial system with splenomegaly and enlargement of tonsils and lymph nodes. Although low HDL cholesterol is associated with an increased risk for coronary artery disease, this condition is not consistently found in TD pedigrees. Metabolic studies in TD patients have revealed a rapid catabolism of HDL and its precursors. In contrast to normal mononuclear phagocytes (MNP), MNP from TD individuals degrade internalized HDL in unusual lysosomes, indicating a defect in cellular lipid metabolism. HDL-mediated cholesterol efflux and intracellular lipid trafficking and turnover are abnormal in TD fibroblasts, which have a reduced in vitro growth rate. The TD locus has been mapped to chromosome 9q31. Here we present evidence that TD is caused by mutations in ABC1, encoding a member of the ATP-binding cassette (ABC) transporter family, located on chromosome 9q22-31. We have analysed five kindreds with TD and identified seven different mutations, including three that are expected to impair the function of the gene product. The identification of ABC1 as the TD locus has implications for the understanding of cellular HDL metabolism and reverse cholesterol transport, and its association with premature cardiovascular disease.
1,539 citations
TL;DR: None of the variants were significantly associated with plasma HDL-C concentrations in either population; however, in VA-HIT, the G3456C variant was associated with a significantly increased risk for CHD end points, suggesting a role for this variant in the premature CHD observed in this population.
97 citations
TL;DR: In this article, the existence of 13 mt-RNR2-like nuclear loci predicted to maintain the open reading frames of 15 distinct full-length HN-like peptides was investigated.
94 citations
TL;DR: It is demonstrated here that the ATP-binding cassette (ABC) transporter ABCA1 is induced during differentiation of human monocytes into macrophages, indicating a dual regulatory function for ABCA 1 in macrophage lipid metabolism and inflammation.
Abstract: Activated lipid-laden macrophages in the vascular wall are key modulators of the inflammatory processes underlying atherosclerosis. We demonstrate here that the ATP-binding cassette (ABC) transporter
80 citations
Journal Article•
TL;DR: Evidence and hypotheses about the new pathophysiological aspects of PPARs activation are reviewed and it is shown that both PPARa and PPARg activation reveal cardio-protective effect in hypertension-induced cardiac hypertrophy.
Abstract: Peroxisome proliferator activated receptors (PPARs) belong to a subfamily of transcription nuclear factors. Three isoforms of PPARs have been identified: alpha, beta/delta and gamma, encoded by different genes and distributed in various tissues. They play important roles in metabolic processes like regulation of glucose and lipid redistribution. They also have anti-atherogenic, anti-inflammatory as well as anti-hypertensive functions. In hypertension-induced cardiac hypertrophy, both PPARa and PPARg activation reveal cardio-protective effect. Despite these beneficial functions, several recent experimental reports point to the possibille unfavorable effects of PPARs activation in lipid metabolism (lipotoxicity) in cardiomyocytes, which can lead to pathologic cardiac hypertrophy in such diseases as diabetes type 2, metabolic syndrome or obesity. This paper reviews evidences and hypotheses about the new pathophysiological aspects of PPARs activation.
50 citations
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TL;DR: Elevated levels of serum cholesterol are probably unique through the hepatic LDL receptor pathway, as evi-in being sufficient to drive the development of athero-denced by the fact that lack of functional LDL receptors sclerosis in humans and experimental animals, even in is responsible for the massive accumulation of LDL in the absence of other known risk factors.
2,995 citations
TL;DR: A review of the basic neuroscience processes of pain (the bio part of biopsychosocial, as well as the psychosocial factors, is presented) and on the development of new technologies, such as brain imaging, that provide new insights into brain-pain mechanisms.
Abstract: The prevalence and cost of chronic pain is a major physical and mental health care problem in the United States today. As a result, there has been a recent explosion of research on chronic pain, with significant advances in better understanding its etiology, assessment, and treatment. The purpose of the present article is to provide a review of the most noteworthy developments in the field. The biopsychosocial model is now widely accepted as the most heuristic approach to chronic pain. With this model in mind, a review of the basic neuroscience processes of pain (the bio part of biopsychosocial), as well as the psychosocial factors, is presented. This spans research on how psychological and social factors can interact with brain processes to influence health and illness as well as on the development of new technologies, such as brain imaging, that provide new insights into brain-pain mechanisms.
2,566 citations
TL;DR: An "oxidative response to inflammation" model is proposed as a means of reconciling the response-to-injury and oxidative modification hypotheses of atherosclerosis.
Abstract: This review focuses on the role of oxidative processes in atherosclerosis and its resultant cardiovascular events. There is now a consensus that atherosclerosis represents a state of heightened oxidative stress characterized by lipid and protein oxidation in the vascular wall. The oxidative modification hypothesis of atherosclerosis predicts that low-density lipoprotein (LDL) oxidation is an early event in atherosclerosis and that oxidized LDL contributes to atherogenesis. In support of this hypothesis, oxidized LDL can support foam cell formation in vitro, the lipid in human lesions is substantially oxidized, there is evidence for the presence of oxidized LDL in vivo, oxidized LDL has a number of potentially proatherogenic activities, and several structurally unrelated antioxidants inhibit atherosclerosis in animals. An emerging consensus also underscores the importance in vascular disease of oxidative events in addition to LDL oxidation. These include the production of reactive oxygen and nitrogen species by vascular cells, as well as oxidative modifications contributing to important clinical manifestations of coronary artery disease such as endothelial dysfunction and plaque disruption. Despite these abundant data however, fundamental problems remain with implicating oxidative modification as a (requisite) pathophysiologically important cause for atherosclerosis. These include the poor performance of antioxidant strategies in limiting either atherosclerosis or cardiovascular events from atherosclerosis, and observations in animals that suggest dissociation between atherosclerosis and lipoprotein oxidation. Indeed, it remains to be established that oxidative events are a cause rather than an injurious response to atherogenesis. In this context, inflammation needs to be considered as a primary process of atherosclerosis, and oxidative stress as a secondary event. To address this issue, we have proposed an "oxidative response to inflammation" model as a means of reconciling the response-to-injury and oxidative modification hypotheses of atherosclerosis.
2,518 citations
TL;DR: The ATP-binding cassette (ABC) transporters are essential for many processes in the cell and mutations in these genes cause or contribute to several human genetic disorders including cystic fibrosis, neurological disease, retinal degeneration, cholesterol and bile transport defects, anemia, and drug response.
2,159 citations
TL;DR: This Review focuses on the role of immune mechanisms in the formation and activation of atherosclerotic plaques, and also includes a discussion of the use of inflammatory markers for predicting cardiovascular events.
Abstract: Immune responses participate in every phase of atherosclerosis. There is increasing evidence that both adaptive and innate immunity tightly regulate atherogenesis. Although improved treatment of hyperlipidaemia reduces the risk for cardiac and cerebral complications of atherosclerosis, these remain among the most prevalent of diseases and will probably become the most common cause of death globally within 15 years. This Review focuses on the role of immune mechanisms in the formation and activation of atherosclerotic plaques, and also includes a discussion of the use of inflammatory markers for predicting cardiovascular events. We also outline possible future targets for prevention, diagnosis and treatment of atherosclerosis.
2,126 citations