Assessment of Gene Expression Profiles in Peripheral Occlusive Arterial Disease

Bubenek, Şerban; Năstase, Anca; Niculescu, A.; Băilă, Sorin; Herlea, Vlad; Lazar, V; Paslaru, Liliana; Botezatu, Anca; Tomescu, Dana; Popescu, Irinel; Dima, Simona

doi:10.1016/j.cjca.2012.03.013

Cited by 15 publications

(11 citation statements)

References 30 publications

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“…17 In addition, lumican has been shown to be expressed in intimal vascular SMCs in human coronary atherosclerosis 18 and, as compared to arteries from healthy subjects, overexpressed in arteries from patients with coronary artery dis-ease, 19 in femoral arteries with atherosclerotic plaques from patients with peripheral occlusive arterial disease 20 and in aortic valves from patients with degenerative aortic stenosis 21 .…”

Section: Discussionmentioning

confidence: 99%

“…Our previous results suggesting that fibromodulin is involved in plaque development by affecting ECM structure and lipid retention, together with previous publications discussing lumican expression in healthy and pathological vasculature, [17][18][19][20][21] raise the question of possible contribution by these SLRPs to atherosclerotic plaque development and its stability. In the present study we have thus for the first time analyzed the expression of fibromodulin and lumican in human carotid plaques in relation to the occurrence of preoperative cerebrovascular symptoms (namely strokes, transient ischemic attacks (TIA) or amaurosis fugax) and postoperative cardiovascular (CV) events.…”

Section: Introductionmentioning

confidence: 99%

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Expression of fibromodulin in carotid atherosclerotic plaques is associated with diabetes and cerebrovascular events

et al. 2015

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Expression of fibromodulin in carotid atherosclerotic plaques is associated with diabetes and cerebrovascular events.Shami, Annelie; Tengryd, Christoffer; Asciutto, Giuseppe; Bengtsson, Eva; Nilsson, Jan; Hultgårdh, Anna; Goncalves, Isabel Link to publication Citation for published version (APA): Shami, A., Tengryd, C., Asciutto, G., Bengtsson, E., Nilsson, J., Hultgårdh, A., & Goncalves, I. (2015). Expression of fibromodulin in carotid atherosclerotic plaques is associated with diabetes and cerebrovascular events. Atherosclerosis, 241(2), 701-708. DOI: 10.1016701-708. DOI: 10. /j.atherosclerosis.2015 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ABSTRACTAims The small leucine-rich proteoglycans fibromodulin and lumican are functionally related extracellular matrix proteins involved in the regulation of collagen fiber formation. Fibromodulin-deficient apolipoprotein E-null mice have decreased vascular retention of lipids and reduced development of atherosclerosis suggesting that fibromodulin may influence the disease process. The aim of the present study was to investigate if fibromodulin and lumican are expressed in human carotid plaques and to determine if their expression is associated with the occurrence of preoperative symptoms and with risk for postoperative cardiovascular events.Methods and Results 153 plaques (51% symptomatic) obtained by carotid endarterectomy were included in this study. Plaque content was analyzed by immunohistochemistry and plaque cytokine content by multiplex technology. Fibromodulin and lumican were widely expressed in plaques and fibromodulin expression was significantly higher in symptomatic plaques. Expression of fibromodulin was significantly higher in plaques obtained from patients with diabetes and a high fibromodulin expression was associated with a higher incidence of post-operative cerebrovascular events, whereas no such associations were seen for lumican. Fibromodulin expression also correlated with plaque lipids and several pro-inflammatory cytokines. In addition, fibromodulin expression correlated with low levels of smooth muscle cells and the antiinflammatory cytokine IL-10.Conclusions These observations support previous experimental findings in mice for a role of fibromodulin in atherosclerosis and provide clinical evidence of the involvement of fibromodulin in the inflammatory processes that characterize atherosclerotic plaque vulnerability. They also suggest that this is of particular importance in diabetes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of fibromodulin in carotid atherosclerotic plaques is associated with diabetes and cerebrovascular events

et al. 2015

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“…However, fibromodulin levels were similar in the two types of arteries [75]. On the other hand, LUM gene expression was elevated in arteries from patients with coronary artery disease compared to healthy control subjects [76], as well as in femoral arteries with atherosclerotic plaques from patients with peripheral occlusive arterial disease [77] and in aortic valves from patients with degenerative aortic stenosis [78]. In addition, lumican and fibromodulin was detected in carotid atherosclerotic plaques from symptomatic and asymptomatic patients (A Hultg ardh-Nilsson A, unpublished data).…”

Section: Lumican (Lum) and Fibromodulin (Fmod)mentioning

confidence: 92%

The small leucine‐rich repeat proteoglycans in tissue repair and atherosclerosis

2015

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Proteoglycans consist of a protein core with one or more covalently attached glycosaminoglycan (GAG) side chains, and have multiple roles in the initiation and progression of atherosclerosis. Here we discuss the potential and known functions of a group of small leucine-rich repeat proteoglycans (SLRPs) in atherosclerosis. We focus on five SLRPs, decorin, biglycan lumican, fibromodulin, and PRELP, because these have been detected in atherosclerotic plaques or demonstrated to have a role in animal models of atherosclerosis. Decorin and biglycan are modified post translationally by substitution with chondroitin/dermatan sulfate GAGs, whereas lumican, fibromodulin, and PRELP have keratan sulfate side chains, and the core proteins have leucine-rich repeat (LRR) motifs that are characteristic of the LRR superfamily. The chondroitin/dermatan sulfate GAG side chains have been implicated in lipid retention in atherosclerosis. The core proteins are discussed here in the context of: (i) interactions with collagens and their implications in tissue integrity, fibrosis, and wound repair; and (ii) interactions with growth factors, cytokines, pathogen-associated molecular patterns, and cell surface receptors that impact normal physiology and disease processes such as inflammation, innate immune responses, and wound healing (i.e processes that are all important in plaque development and progression). Thus, studies of these SLRPs in the context of wound healing are providing clues about their functions that may be important in early stages of atherosclerosis to plaque vulnerability and cardiovascular disease at later stages. Understanding of signal transduction pathways regulated by the core protein interactions is leading to novel roles and therapeutic potential for these proteins in wound repair and atherosclerosis.

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“…Additionally, when NNMT catalyzes the methylation of nicotinamide, S-adenosyl homocysteine (SAH) and homocysteine (Hcy) are generated [10]. Hyperhomocysteinemia is one of the independent risk factors for cardiovascular diseases [11]; therefore, the relationship between NNMT and cardiovascular diseases has recently been increasingly reported [12–14]. …”

Section: Introductionmentioning

confidence: 99%

“…Bubenek et al [14] reported that the occurrence and development of peripheral arterial occlusive diseases were closely related to NNMT expression and the serum NNMT level, and the NNMT expression level was significantly positively correlated with the low density lipoprotein level and significantly negatively correlated with the high density lipoprotein level. At present, more than 200 NNMT single nucleotide polymorphisms (SNPs) in noncoding region have been identified in the human genome projects, but only one SNP (rs694539) has been reported in the genetic association studies.…”

Section: Introductionmentioning

confidence: 99%

Physiological Study on Association between Nicotinamide N-Methyltransferase Gene Polymorphisms and Hyperlipidemia

Zhu

Lin

Chen

et al. 2016

BioMed Research International

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Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide. Our previous works indicate that NNMT is involved in the body mass index and energy metabolism, and recently the association between a SNP (rs694539) of NNMT and a variety of cardiovascular diseases was reported. At present, more than 200 NNMT single nucleotide polymorphisms (SNPs) have been identified in the databases of the human genome projects; however, the association between rs694539 variation and hyperlipidemia has not been reported yet, and whether there are any SNPs in NNMT significantly associated with hyperlipidemia is still unclear. In this paper, we selected 19 SNPs in NNMT as the tagSNPs using Haploview software (Haploview 4.2) first and then performed a case-control study to observe the association between these tagSNPs and hyperlipidemia and finally applied physiological approaches to explore the possible mechanisms through which the NNMT polymorphism induces hyperlipidemia. The results show that a SNP (rs1941404) in NNMT is significantly associated with hyperlipidemia, and the influence of rs1941404 variation on the resting energy expenditure may be the possible mechanism for rs1941404 variation to induce hyperlipidemia.

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Assessment of Gene Expression Profiles in Peripheral Occlusive Arterial Disease

Cited by 15 publications

References 30 publications

Expression of fibromodulin in carotid atherosclerotic plaques is associated with diabetes and cerebrovascular events

Expression of fibromodulin in carotid atherosclerotic plaques is associated with diabetes and cerebrovascular events

The small leucine‐rich repeat proteoglycans in tissue repair and atherosclerosis

Physiological Study on Association between Nicotinamide N-Methyltransferase Gene Polymorphisms and Hyperlipidemia

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