Serum Angiopoietin-like Protein 3 Levels: Possible Correlation with Progressive Skin Sclerosis, Digital Ulcers and Pulmonary Vascular Involvement in Patients with Systemic Sclerosis

Ichimura, Yohei; Asano, Yoshihide; Akamata, Kaname; Aozasa, Naohiko; Noda, Shinichi; Taniguchi, Takashi; Takahashi, Takehiro; Toyama, Tetsuo; Sumida, Hitoshi; Kuwano, Yosihiro; Yanaba, Koichi; Tada, Yayoi; Sugaya, Makoto; Sato, Shinichi; Kadono, Takafumi

doi:10.2340/00015555-1680

Cited by 10 publications

(3 citation statements)

References 19 publications

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“…The role of fatty acid oxidation in PAH is further emphasized in a study showing that mice lacking the gene for the metabolic enzyme malonyl‐coenzyme A decarboxylase (MCD), an enzyme involved in fatty acid oxidation, do not develop PAH during chronic hypoxia 45 . Studies have shown that serum levels of secreted glycoproteins involved in lipid metabolism and angiogenesis, such as angiopoietin‐like protein 3 (ANGPTL3), are positively correlated with RVSPs and could contribute to PAH in systemic sclerosis 46 . In summary, abnormal cellular metabolism and impaired mitochondrial function could play an important role in the pathogenesis of PAH (Fig.…”

Section: Oxidative Stress and Impaired Mitochondrial Function In The Pathogenesis Of Pah And Associated Rv Failurementioning

confidence: 99%

“…45 Studies have shown that serum levels of secreted glycoproteins involved in lipid metabolism and angiogenesis, such as angiopoietin-like protein 3 (ANGPTL3), are positively correlated with RVSPs and could contribute to PAH in systemic sclerosis. 46 In summary, abnormal cellular metabolism and impaired mitochondrial function could play an important role in the pathogenesis of PAH (Fig. 2).…”

Section: Oxidative Stress and Impaired Mitochondrial Function In The mentioning

confidence: 99%

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Role of Oxidized Lipids in Pulmonary Arterial Hypertension

et al. 2016

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Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by interplay of many cellular, molecular, and genetic events that lead to excessive proliferation of pulmonary cells, including smooth muscle and endothelial cells; inflammation; and extracellular matrix remodeling. Abnormal vascular changes and structural remodeling associated with PAH culminate in vasoconstriction and obstruction of pulmonary arteries, contributing to increased pulmonary vascular resistance, pulmonary hypertension, and right ventricular failure. The complex molecular mechanisms involved in the pathobiology of PAH are the limiting factors in the development of potential therapeutic interventions for PAH. Over the years, our group and others have demonstrated the critical implication of lipids in the pathogenesis of PAH. This review specifically focuses on the current understanding of the role of oxidized lipids, lipid metabolism, peroxidation, and oxidative stress in the progression of PAH. This review also discusses the relevance of apolipoprotein A-I mimetic peptides and microRNA-193, which are known to regulate the levels of oxidized lipids, as potential therapeutics in PAH.

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Section: Oxidative Stress and Impaired Mitochondrial Function In The Pathogenesis Of Pah And Associated Rv Failurementioning

confidence: 99%

Section: Oxidative Stress and Impaired Mitochondrial Function In The mentioning

confidence: 99%

Role of Oxidized Lipids in Pulmonary Arterial Hypertension

et al. 2016

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“…To date, there are no studies in which the ANGPTL4 level in SSc has been assessed. However, ANGPTL4 and ANGPTL3 share numerous features, and the level of ANGPTL3 has been found to be increased in patients with SSc, and associated with the prevalence of digital ulcers, suggesting the involvement of ANGPTL3 in the pathogenesis of SSc-associated microangiopathy (30). In this regard, clarifying the role of ANGPTLs in SSc may lead to further understanding of the complex SSc pathogenesis.…”

Section: Hypoxia In Systemic Sclerosis: the Hif Pathway And Its Dysrementioning

confidence: 99%

Acroosteolysis in systemic sclerosis: An insight into hypoxia-related pathogenesis

Siao-Pin

Damian

Muntean

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Acro-osteolysis, or bony resorption of the terminal digital tufts, is a well-recognized, but under-researched, feature of systemic sclerosis. The mechanisms that disturbs local homeostatic balance of bone formation and resorption in favor of osteoclast activation and pathological bone loss remain to be established. Vascular alterations and reduced capillary density impair tissue oxygenation in systemic sclerosis, and the resulting hypoxia might contribute directly to the disease progression. In this paper we summarize the current evidence for hypoxia as the common pathophysiological denominator of digital vasculopathy and enhanced osteoclastic activity in systemic sclerosis-associated acroosteolysis. The hypoxia-inducible transcription factor HIF-1α and VEGF signaling has a critical role in regulating osteoclastic bone-resorption and angiogenesis, and increased osteoclastogenesis and higher VEGF levels may contribute to acroosteolysis in systemic sclerosis. The cells of the osteoblast lineage also have important roles in angiogenic-osteogenic coupling. The research in this field might help limiting the disability associated with the disease.

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Impaired angiogenesis as a feature of digital ulcers in systemic sclerosis

et al. 2016

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Impaired angiogenesis in systemic sclerosis has a major role in tissue injury pathogenesis. Our objective was to determine whether angiogenic biomarkers (vascular endothelial growth factor (VEGF), endoglin, and endostatin) are related to microvascular damage and to determine their predictive value for new digital ulcers (DU). The main outcome of the study was the occurrence of a new digital ulcer during 3-year follow-up. This prospective longitudinal study was performed between October 2011 and December 2014. Seventy-seven patients definitely diagnosed with systemic sclerosis where divided into two groups: those with active DU at baseline and those with no DU until enrollment. Patients were matched by sex and age with healthy controls. Serum levels of VEGF, endoglin, and endostatin were measured at enrollment, and several nailfold videocapillaroscopies were performed during the 3-year follow-up. Serum levels of VEGF were lower (245.06, 158.68-347.33; p < 0.001) and those of endoglin were higher (3.013, 1.463-7.023; p < 0.001) in patients with active DU than those with no DU history (339.49, 202.00-730.93/1.879, 0.840-3.280), and they were higher than those found in controls (178.030, 101.267-222.102)/0.277, 0.154-0.713), respectively. No differences in endostatin levels were found between groups (p = 0.450). Endoglin was the only biomarker significantly different (p = 0.031) between patients with diffuse versus limited systemic sclerosis and between early, active, and late patterns (p = 0.020). VEGF was identified as an independent predictor for the development of new DU. Our study confirmed the relationship between angiogenic vascular biomarkers and the occurrence of DU. Endoglin and VEGF serum levels are potential risk factors, and VEGF has a predictive value for the occurrence of new DU.

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Serum Angiopoietin-like Protein 3 Levels: Possible Correlation with Progressive Skin Sclerosis, Digital Ulcers and Pulmonary Vascular Involvement in Patients with Systemic Sclerosis

Cited by 10 publications

References 19 publications

Role of Oxidized Lipids in Pulmonary Arterial Hypertension

Role of Oxidized Lipids in Pulmonary Arterial Hypertension

Acroosteolysis in systemic sclerosis: An insight into hypoxia-related pathogenesis

Impaired angiogenesis as a feature of digital ulcers in systemic sclerosis

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