1.
Coronary and peripheral artery plaques: do differences in plaque characteristics translate to differences in lipid management?
Tsai, S, Vega, GL
Journal of investigative medicine : the official publication of the American Federation for Clinical Research. 2020;(6):1141-1151
Abstract
Optimal medical management of patients with peripheral arterial disease (PAD) includes statin therapy, which has been shown to decrease the risk of major cardiovascular events. However, the relationship between low-density lipoprotein (LDL) lowering, PAD progression and limb outcomes remains controversial. Although prevention of coronary and cerebrovascular events is a priority, limb outcomes are still important determinants of quality of life and healthcare spending. This review will highlight differences between coronary artery disease (CAD) and PAD, and in particular, the more prevalent role of lipids and LDL cholesterol in CAD versus calcification in PAD. This difference may contribute to the differential impact of LDL cholesterol levels on coronary events and outcomes versus limb outcomes. Beyond LDL lowering, immune modulators have emerged as another agent to treat atherosclerosis in CAD, however similar data in PAD are lacking. Small studies have suggested that other lipids besides LDL cholesterol, such as triglycerides or small dense LDL, may have a greater impact on limb outcomes in patients with PAD. Although statin therapy is central in the management of patients with PAD, current understanding of the distinctions between PAD and CAD suggest that there may be other non-LDL targets for risk reduction that require further study.
2.
HIV vasculopathy: role of mononuclear cell-associated Krüppel-like factors 2 and 4.
Hale, AT, Longenecker, CT, Jiang, Y, Debanne, SM, Labatto, DE, Storer, N, Hamik, A, McComsey, GA
AIDS (London, England). 2015;(13):1643-50
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Abstract
OBJECTIVE To determine the relationships between Krüppel-like factors (KLF) 2 and 4, immune-activation, and subclinical vascular disease in HIV-infected patients on antiretroviral therapy (ART). DESIGN Double-blind, randomized, placebo-controlled trial. METHODS We studied 74 HIV-infected adults on ART enrolled in a randomized clinical trial of statin therapy. KLF2 and KLF4 gene expression was measured by quantitative PCR from peripheral blood mononuclear cells (PBMCs) at baseline and after 24 weeks of 10 mg daily rosuvastatin or placebo. At the same time points, T-cell and monocyte activation were assessed by flow cytometry and vascular health was assessed by cardiac computed tomography and carotid ultrasound. RESULTS KLF4 expression was negatively correlated with duration of ART (r = -0.351, P = 0.004) and positively correlated with measures of immune activation: proinflammatory monocytes [CD14CD16 (r = 0.343, P = 0.003)], patrolling monocytes [CD14CD16 (r = 0.276, P = 0.017)], and activated CD8 T-lymphocytes [CD8DRCD38 (r = 0.264, P = 0.023)]. KLF2 expression was negatively correlated with subclinical atherosclerosis: mean-mean common carotid artery intima-media thickness (r = -0.231, P = 0.048), mean-max carotid artery intima-media thickness (r = -0.271, P = 0.020), and coronary artery calcium score (r = -0.254, P = 0.029). There were no statistically significant changes in KLF2/4 expression in PBMCs after 24 weeks of rosuvastatin. CONCLUSION Expression of KLF4 in PBMCs positively correlates with cellular markers of immune activation, whereas KLF2 expression negatively correlates with markers of subclinical atherosclerosis in this HIV-infected population on ART. Additional studies are needed to determine if targeted interventions might alter KLF2/4 expression to reduce inflammation and vascular risk in humans.
3.
Hyperlipidemia: a risk factor for chronic allograft dysfunction.
Castelló, IB
Kidney international. Supplement. 2002;(80):73-7
Abstract
While the early results of renal transplantation have improved in the last years, but the long-term allograft survival have not improved to the same extent. The major cause of these graft losses is chronic allograft dysfunction (CAD). The pathogenesis of CAD is complex and results from a interaction of immune and nonimmune factors. Between these non-immunological related factors there are two cardiovascular risk factors, hypertension and especially hyperlipidemia, that have been implicated in the development and progression of CAD. Lipid profile abnormalities are very prevalent in renal transplant patients. In last years several authors have reported an association between different lipid profile alterations and CAD. We conducted an observational study in our group to determine the relationship between different lipid disturbances and CAD. The hypertriglyceridemia and the Lp(a)>30 mg/dL before and after transplantation were, between the lipid abnormalities, the two independent risk factors for CAD in a multivarite analysis.