A retrospective claims analysis: Compliance and discontinuation rates among Canadian patients with multiple sclerosis treated with disease-modifying therapies.

Background: Compliance to disease modifying therapy (DMT) is associated with a reduced risk of relapse, lower healthcare resource utilization, and improved health-related quality of life in patients with multiple sclerosis (MS). Our objective was to assess the compliance and discontinuation rates of fingolimod relative to other oral, injectable, and infusible DMTs available on the market at the time of the study in Canada in patients with relapsing-remitting MS (RRMS).

Methods And Findings: We conducted a retrospective claims analysis.

The impact of treatment adherence on clinical and economic outcomes in multiple sclerosis: Real world evidence from Alberta, Canada.

Background: Approximately 1 in 400 Albertans has multiple sclerosis (MS). The current study objective was to determine the real-world impact of adherence to disease-modifying therapies (DMTs) on healthcare utilization and costs among MS patients utilizing administrative data from the Alberta health system in Canada.

Methods: MS patients were identified using a validated case definition (≥ 1 inpatient record or ≥ 5 practitioner claims within 2 years) and the study index DMT was defined as the first claim for a DMT between 1 April 2011 and 31 March 2014.

Reduced expression of let-7f activates TGF-β/ALK5 pathway and leads to impaired ischaemia-induced neovascularization after cigarette smoke exposure.

This study sought to determine the potential role of microRNAs (miRNAs) in the detrimental effects of cigarette smoke on angiogenesis and neovascularization. Using large-scale miRNA profiling and qRT-PCR analyses, we identified let-7f as a pro-angiogenic miRNA which expression is significantly reduced in HUVECs treated with cigarette smoke extracts (CSE), and in the ischemic muscles of mice that are exposed to cigarette smoke (MES). In a mouse model of hindlimb ischaemia, intramuscular injection of let-7f mimic restored ischaemia-induced neovascularization in MES.

Psychological stress impairs ischemia-induced neovascularization: Protective effect of fluoxetine.

Background: Psychological stress (PS) has been associated with the development of cardiovascular diseases and adverse long-term outcomes after ischemic events. However, the precise mechanisms involved are not completely understood. Here we investigated the effect of PS on ischemia-induced neovascularization, and the potential therapeutic effect of fluoxetine in this condition.

Fish oil-enriched diet protects against ischemia by improving angiogenesis, endothelial progenitor cell function and postnatal neovascularization.

Background: Fish oil consumption has been associated with a reduced incidence of cardiovascular diseases. However, the precise mechanisms involved are not completely understood. Here we tested the hypothesis that a fish oil-enriched diet improves neovascularization in response to ischemia.

Protection against vascular aging in Nox2-deficient mice: Impact on endothelial progenitor cells and reparative neovascularization.

Background: Aging is associated with increased oxidative stress levels and impaired neovascularization following ischemia. Because Nox2-containing NADPH oxidase is a major source of ROS in the vasculature, we investigated its potential role for the modulation of ischemia-induced neovascularization in the context of aging.

Methods And Results: Hindlimb ischemia was surgically induced by femoral artery removal in young (2 months) and old (10 months) Nox2-deficient (Nox2(-/-)) and wild type mice.

Accelerated vascular aging in CuZnSOD-deficient mice: impact on EPC function and reparative neovascularization.

Objective: Aging is associated with increased oxidative stress levels and impaired neovascularization following ischemia. CuZnSOD has an important role to limit oxidative stress in the vasculature. Here we investigated the role of CuZnSOD for the modulation of ischemia-induced neovascularisation during aging.

Nox2-derived reactive oxygen species contribute to hypercholesterolemia-induced inhibition of neovascularization: effects on endothelial progenitor cells and mature endothelial cells.

Background: Hypercholesterolemia has been associated with impaired angiogenesis and reduced blood flow recuperation after ischemia. However, the precise mechanisms involved are unknown. Here we investigated the role of Nox2-derived reactive oxygen species (ROS) in the modulation of neovascularization by hypercholesterolemia.

Essential role of copper-zinc superoxide dismutase for ischemia-induced neovascularization via modulation of bone marrow-derived endothelial progenitor cells.

Objective: To investigate the effect of oxidative stress on ischemia-induced neovascularization in copper-zinc (CuZn) superoxide dismutase (SOD)-deficient mice.

Methods And Results: In the vascular wall, CuZnSOD is essential for protecting against excessive oxidative stress and maintaining endothelial function. However, its specific role for the development of new vessels in response to ischemia is unknown.

Sildenafil increases endothelial progenitor cell function and improves ischemia-induced neovascularization in hypercholesterolemic apolipoprotein E-deficient mice.

Hypercholesterolemia is associated with impaired neovascularization in response to ischemia. Potential mechanisms include defective NO bioactivity and a reduction in the number/function of endothelial progenitor cells (EPCs). Here we tested the hypothesis that sildenafil, a phosphodiesterase 5 inhibitor that increases NO-driven cGMP levels, could stimulate EPC function and improve ischemia-induced neovascularization in hypercholesterolemic conditions.

Probucol and antioxidant vitamins rescue ischemia-induced neovascularization in mice exposed to cigarette smoke: potential role of endothelial progenitor cells.

Objective: Cigarette smoking is associated with impaired neovascularization in response to ischemia. Potential mechanisms include increased generation of reactive oxygen species (ROS) and a reduction in the function of endothelial progenitor cells (EPCs). Here we tested the hypothesis that antioxidant therapies could stimulate EPC function and improve ischemia-induced neovascularization following cigarette smoke exposure.

Nox2-containing NADPH oxidase deficiency confers protection from hindlimb ischemia in conditions of increased oxidative stress.

Objective: Because Nox2-containing NADPH oxidase is a major source of ROS in the vasculature, we investigated its potential role for the modulation of ischemia-induced neovascularization in conditions of increased oxidative stress.

Methods And Results: To mimic a clinical situation of increased oxidative stress, mice were exposed to cigarette smoke before and after the surgical induction of hindlimb ischemia. Nox2 expression and oxidative stress in ischemic tissues were significantly increased in wild-type mice, but not in mice deficient for the Nox2-containing NADPH oxidase (Nox2(-/-)).

Moderate consumption of red wine (cabernet sauvignon) improves ischemia-induced neovascularization in ApoE-deficient mice: effect on endothelial progenitor cells and nitric oxide.

Moderate consumption of red wine is associated with a decreased incidence of cardiovascular diseases in populations with relatively high amount of fat in the diet. However, the mechanisms involved in this protective effect are not completely understood. Here we show that moderate consumption of red wine (equivalent to 2 glasses/day in humans) but not ethanol only, improves blood flow recovery by 32% after hindlimb ischemia in hypercholesterolemic ApoE-deficient mice.

Cigarette smoke exposure impairs VEGF-induced endothelial cell migration: role of NO and reactive oxygen species.

Endothelial dysfunction is one of the earliest pathological effects of cigarette smoking. Vascular endothelial growth factor (VEGF) has been shown to be an important regulator of endothelial healing and growth. Accordingly, we tested the hypothesis that cigarette smoke exposure impairs VEGF actions in endothelial cells.

Circulating endothelial progenitor cells from healthy smokers exhibit impaired functional activities.

Objective: Endothelial dysfunction is one of the earliest pathological effects of cigarette smoking. It has recently been suggested that endothelial progenitor cells (EPCs) could contribute to ongoing endothelial maintenance and repair. Accordingly, we tested the hypothesis that cigarette smoking is associated with EPC dysfunction.