The mechanisms of the harmful cardiovascular effects of small particulate matter are incompletely understood. Endothelial progenitor cells (EPCs) predict outcome of patients with vascular disease. ...The aim of our study was to examine the effects of diesel exhaust particles (DEP) on EPC and on the associated vascular damage in mice. C57Bl/6 mice were exposed to DEP. 2 μg DEP/day was applicated intranasally for 3 weeks. Exposure to DEP reduced DiLDL/lectin positive EPC to 58.4 ± 5.6 % (
p
< 0.005). Migratory capacity was reduced to 65.8 ± 3.9 % (
p
< 0.0001). In ApoE
−/−
mice, DEP application reduced the number of EPC to 75.6 ± 6.4 % (
p
< 0.005) and EPC migration to 58.5 ± 6.8 % (
p
< 0.005). Neoangiogenesis was reduced to 39.5 ± 14.6 % (
p
< 0.005). Atherogenesis was profoundly increased by DEP treatment (157.7 ± 18.1 % vs. controls,
p
< 0.05). In cultured human EPC, DEP (0.1–100 μg/mL) reduced migratory capacity to 25 ± 2.6 % (
p
< 0.001). The number of colony-forming units was reduced to 8.8 ± 0.9 % (
p
< 0.001) and production of reactive oxygen species was elevated by DEP treatment (
p
< 0.001). Furthermore, DEP treatment increased apoptosis of EPC (to 266 ± 62 % of control,
p
< 0.05). In a blood–brain barrier model, DEP treatment impaired endothelial cell integrity during oxygen–glucose deprivation (
p
< 0.001). Diesel exhaust particles impair endothelial progenitor cell number and function in vivo and in vitro. The reduction in EPC was associated with impaired neoangiogenesis and a marked increase in atherosclerotic lesion formation.
RD appears to be a safe and effective therapeutic approach to lower blood pressure in patients with resistant hypertension and is associated with favorable effects on renal hemodynamics and urinary ...albumin excretion rate.
Impaired vascular compliance is associated with cardiovascular mortality. The effects of heart rate on vascular compliance are unclear. Therefore, we characterized effects of heart rate reduction ...(HRR) by I(f) current inhibition on aortic compliance and underlying molecular mechanisms in apolipoprotein E-deficient (ApoE(-)/(-)) mice.
ApoE(-)/(-) mice fed a high-cholesterol diet and wild-type (WT) mice were treated with ivabradine (20 mg/kg/d) or vehicle for 6 weeks. Compliance of the ascending aorta was evaluated by MRI.
Ivabradine reduced heart rate by 113 ± 31 bpm (~19%) in WT mice and by 133 ± 6 bpm (~23%) in ApoE(-)/(-) mice. Compared to WT controls, ApoE(-)/(-) mice exhibited reduced distensibility and circumferential strain. HRR by ivabradine increased distensibility and circumferential strain in ApoE(-)/(-) mice but did not affect both parameters in WT mice. Ivabradine reduced aortic protein and mRNA expression of the angiotensin II type 1 (AT1) receptor and reduced rac1-GTPase activity in ApoE(-)/(-) mice. Moreover, membrane translocation of p47(phox) was inhibited. In ApoE(-)/(-) mice, HRR induced anti-inflammatory effects by reduction of aortic mRNA expression of IL-6, TNF-alpha and TGF-beta.
HRR by ivabradine improves vascular compliance in ApoE(-)/(-) mice. Contributing mechanisms include downregulation of the AT1 receptor, attenuation of oxidative stress and modulation of inflammatory cytokine expression.
Abstract Objective Epidemiologic studies suggest that elevated postprandial triglycerides (ppTG) are associated with future cardiovascular events. Monocyte activation plays an important role in ...vascular diseases. Omega-3 fatty acids (n3-FA) lower fasting TG levels. The effects of n3-FA on ppTG and the role of ppTG for monocyte activation are insufficiently understood. Methods and results 23 healthy volunteers and 30 non-diabetic patients with documented coronary artery disease were subjected to an oral TG tolerance test (OTTT) consisting of 80 g cream fat or to water as control (H2 O). Patients were treated with 4 g n3-FA/day or placebo for 3 weeks in a randomized, placebo-controlled, double-blind, crossover study. Relative postprandial TG increase reached its maximum 4 h after fat intake (185.1 ± 10.9% of baseline). n3-FA reduced fasting TG from 137.1 ± 12.9 to 112.2 ± 8.6 mg/dl ( p < 0.05), and maximum ppTG concentrations from 243.6 ± 24.6 to 205.8 ± 17.1 mg/dl ( p < 0.05), while relative TG increase (192.8 ± 12.7%) was comparable to placebo. Relative monocytopenia and neutrophilia were detected following fat intake, which was unaffected by n3-FA and also detectable in the H2 O group. Serum chemotactic cytokine (MCP1 and fractalkine) concentrations and monocyte migration were not affected by fat intake or n3-FA. Monocyte activation markers CD11b and CD14, monocyte subpopulations CD16+ CD14high and CD16+ CD14low , sICAM serum levels and markers of oxidative stress remained unchanged by fat intake or n3-FA. Conclusion The postprandial TG increase does not stimulate monocytes beyond their circadian activation patterns. n3-FA reduce fasting TG and the postprandial TG increase. n3-FA may therefore allow to prospectively study whether selected patients benefit from TG-lowering independent of LDL- and HDL-cholesterol.
Despite advances in nonpharmacologic and pharmacologic therapy, blood pressure control rates in hypertension are low. About 10 % of patients with hypertension fulfill the criteria of therapy ...resistance, which is defined as noncontrolled blood pressure despite treatment with ≥3 antihypertensive drugs of different classes, including a diuretic, at optimal or maximal tolerated doses. Although the pathogenesis of resistant hypertension is multifactorial, an interaction between renal afferent and efferent sympathetic nerves and the central nervous system plays a key role, leading to increased renal and central sympathetic activity. Catheter-based renal sympathetic denervation (RDN) is a novel therapeutic technique for the treatment of resistant hypertension. Clinical trials of RDN have shown a significant and sustained reduction of blood pressure as well as renal and central sympathetic activity. In clinical practice, appropriate patient selection is crucial to ensure successful and safe treatment. Beyond hypertension, RDN was associated with reduction of heart rate, regression of left ventricular mass, and improvements in glucose metabolism and severity of sleep apnea. Further studies addressing open questions in the treatment of resistant hypertension and evaluating potential new indications such as metabolic syndrome or heart failure (RE-ADAPT-HF) are necessary to prove effectiveness and safety of RDN in these patients. By modulating sympathetic activity, RDN has the potential to provide benefit in a variety of diseases, but these concepts have to be evaluated in well-designed prospective controlled clinical trials.
PDF
