Insulin resistance in pulmonary arterial hypertension

Zamanian, Roham T.; Hansmann, Georg; Snook, S.; Lilienfeld, David E.; Rappaport, Karen M; Reaven, Gerald M.; Rabinovitch, Marlene; Doyle, Ramona L.

doi:10.1183/09031936.00000508

Cited by 249 publications

(296 citation statements)

References 55 publications

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“…76 Metabolic syndrome and insulin resistance are associated with low circulating HDL-C levels and may predispose to the development of pulmonary vascular disease. 77,78 Indeed, insulin resistance and RV hypertrophy with pulmonary vascular remodeling are observed in an apolipoprotein E-deficient mouse model. 79 In addition, depressed circulating levels of HDL-C are associated with worse clinical outcomes in PAH patients and are independent of other cardiovascular risk factors.…”

Section: Plasma Hdl and Pahmentioning

confidence: 99%

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: Plasma Hdl and Pahmentioning

confidence: 99%

Role of Oxidized Lipids in Pulmonary Arterial Hypertension

et al. 2016

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“…An emerging body of evidence suggests that the metabolic syndrome and insulin resistance may predispose to pulmonary vascular disease (17)(18)(19)(20). An apolipoprotein E-deficient mouse model on a highfat diet developed insulin resistance, pulmonary vascular remodeling, and right ventricular hypertrophy, changes that were reversed by rosiglitazone, an insulin-sensitizer drug (17).…”

mentioning

confidence: 99%

Plasma Levels of High-Density Lipoprotein Cholesterol and Outcomes in Pulmonary Arterial Hypertension

Heresi¹,

Aytekin²,

Newman³

et al. 2010

Am J Respir Crit Care Med

115

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Rationale: High-density lipoprotein cholesterol (HDL-C) promotes healthy vascular function, and it is decreased in insulin resistance. Insulin resistance predisposes to pulmonary vascular disease. Objectives: We hypothesized that HDL-C is associated with clinical outcomes in pulmonary arterial hypertension (PAH). Methods: Plasma HDL-C concentrations were measured in 69 patients with PAH (age, 46.7 6 12.9 yr; female, 90%) and 229 control subjects (age, 57 6 13 yr; female, 48%). Clinical outcomes of interest included hospitalization for PAH, lung transplantation, and all-cause mortality. Survival and time to clinical worsening curves were derived by the Kaplan-Meier method. Cox regression modeling of outcome versus HDL-C with individual covariate adjustments was performed. Measurement and Main Results: HDL-C was low in subjects with PAH compared with control subjects (median, interquartile range: PAH: 36, 29-40 mg/dl; control subjects: 49, 40-60 mg/dl; P , 0.001). An HDL-C level of 35 mg/dl discriminated survivors from nonsurvivors, with a sensitivity of 100% and specificity of 60%. After a median follow-up of 592 days, high HDL-C was associated with decreased mortality (hazard ratio for every 5-mg/dl increase in HDL-C, 0.643; 95% confidence interval, 0.504-0.822; P 5 0.001) and less clinical worsening (hazard ratio for every 5-mg/dl increase in HDL-C, 0.798; 95% confidence interval, 0.663-0.960; P 5 0.02). HDL-C remained a significant predictor of survival after adjusting for cardiovascular risk factors, C-reactive protein, indices of insulin resistance, and severity of PAH (all P , 0.05). Conclusions: Low plasma HDL-C is associated with higher mortality and clinical worsening in PAH. This association does not appear to be explained by underlying cardiovascular risk factors, insulin resistance, or the severity of PAH.

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“…Potential environmental risk factors and disease modifiers such as cigarette smoke exposure [18], hormonal and metabolic abnormalities such as hyperandrogenaemia, dyslipidaemia and insulin resistance [19,20], have been identified in adults with PAH recently, and should be studied systematically in children. However, sufficient recruitment of PAH children into classical randomised controlled trials (RCTs) is particular difficult.…”

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confidence: 99%

Registries for paediatric pulmonary hypertension

Hansmann

Hoeper

2013

Eur Respir J

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@ERSpublications Paediatric pulmonary arterial hypertension should be treated specifically and differently from adult pulmonary arterial hypertension http://ow.ly/mzPDT Pulmonary arterial hypertension (PAH) is a progressive, angio-obliterative disease leading to increased pulmonary vascular resistance, right heart failure, and death in ,25-60% of PAH patients 5 years after diagnosis [1][2][3]. The estimated prevalence of PAH is 15-50 cases per million adults [4-6] and 2-16 cases per million children [7][8][9]. In certain at-risk groups, however, the occurrence of PAH is substantially higher. For example, the prevalence is 0.5% in HIV-infected patients [10] and 4-6% in schistosomiasis [11]. These diseases are far more common in developing countries with limited health care and, thus, the real burden of PAH worldwide is probably underestimated.Historically, extrapolation from adult pulmonary hypertension studies has been used to make assumptions on the disease in children; however, this approach is neither validated nor appropriate [12]. The recent comprehensive analysis of paediatric registries allowed predictions on the epidemiology, clinical practice and outcome of PAH in childhood. In France, for example, the prevalence of paediatric PAH was estimated to be 2.2 cases per million children [7]. In the UK, the incidence and prevalence of idiopathic PAH (IPAH) was 0.48 and 2.1 per million children, respectively [8]. In the Netherlands, the incidence and prevalence of IPAH was 0.7 and 4.4 per million children, whereas PAH associated with congenital heart disease (PAH-CHD) had an incidence of 2.2 and prevalence of 15.6 per million [9]. Of note, the PAH disease spectrum may somewhat differ in the individual tertiary centre and in multicentre registries [13]. In a British cohort study, the 5-year survival for children with IPAH was only 75% with a freedom from death or transplantation of only 57% (1986 and 2000 with follow-up to 2007) [8].Patients, family members and healthcare providers should be aware of the unique features of paediatric pulmonary hypertensive vascular disease (PPHVD) [14,15]. These include the fetal origins, developmental and adaptive aspects of pulmonary vascular disease (PVD) and right ventricular dysfunction (RVD) in both childhood-and adult-onset disease. The proposal for a new classification of PPHVD (Panama, 2011 [14]) aims to incorporate such specific paediatric aspects that are not adequately addressed in the current classification of pulmonary hypertension (Dana Point, CA, USA, 2008) [16]. The Panama proposal of PPHVD is still very new, not broadly (internationally) accepted yet, and probably will undergo further modifications, according to international meetings (e.g., the PH World Symposium, Nice, France, 2013) and feedback from healthcare providers.

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Insulin resistance in pulmonary arterial hypertension

Cited by 249 publications

References 55 publications

Role of Oxidized Lipids in Pulmonary Arterial Hypertension

Role of Oxidized Lipids in Pulmonary Arterial Hypertension

Plasma Levels of High-Density Lipoprotein Cholesterol and Outcomes in Pulmonary Arterial Hypertension

Registries for paediatric pulmonary hypertension

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