Vascular pharmacology
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Vascular pharmacology · Dec 2006
2-Methoxyestradiol mediates the protective effects of estradiol in monocrotaline-induced pulmonary hypertension.
When exposed to chronic hypoxia or toxin monocrotaline (MCT), female animals develop less severe pulmonary arterial hypertension (PH) compared to males; ovariectomy (OVX) exacerbates PH, and OVX animals treated with estradiol (E2) develop less severe disease. There is a line of evidence suggesting that cardiovascular protective effects of E2 are mediated by its major metabolite, 2-methoxyestradiol (2ME). Recently, we have shown that 2ME attenuates the development and retards the progression of MCT-induced pulmonary hypertension in male rats. ⋯ In diseased OVX rats, treatment with 2ME prevented the worsening of PH and attenuated the inflammatory response and vascular remodeling. No mortality was recorded in the OVX-MCT+2ME group vs. 10% and 36% mortality in the MCT and OVX-MCT group, respectively. This study suggests that 2-methoxyestradiol (a major non-estrogenic metabolite of E2) may mediate the protective effects of estradiol in MCT-induced PH, and warrants further evaluation of 2ME for treatment of PH.
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Pentraxins are a family of evolutionarily conserved multifunctional pattern-recognition proteins characterized by a cyclic multimeric structure. Based on the primary structure of the subunit, the pentraxins are divided into two groups: short pentraxins and long pentraxins. C-reactive protein (CRP) and serum amyloid P-component (SAP) are the two short pentraxins. ⋯ PTX3 interacts with several ligands, including growth factors, extracellular matrix components and selected pathogens, playing a role in complement activation and facilitating pathogen recognition by phagocytes, acting as a predecessor of antibodies. In addition, PTX3 is essential in female fertility by acting as a nodal point for the assembly of the cumulus oophorus hyaluronan-rich extracellular matrix. Thus, the prototypic long pentraxin PTX3 is a multifunctional soluble pattern recognition receptor acting as a non-redundant component of the humoral arm of innate immunity and involved in tuning inflammation, in matrix deposition and female fertility.
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Vascular pharmacology · Jul 2006
ReviewPeroxisome proliferator-activated receptors in vascular biology-molecular mechanisms and clinical implications.
Peroxisome proliferator-activated receptors (PPAR)alpha, gamma and beta/delta belong to the nuclear receptor family of ligand-activated transcription factors. PPARs heterodimerize with the retinoid X receptor (RXR) and then act as transcription factors to modulate the function of many target genes. PPARalpha, gamma and beta/delta subtypes have significant differences in their ligand and gene specificities. ⋯ PPAR agonists slightly reduce blood pressure are cardio-protective and correct vascular structure and endothelial dysfunction in experimental models of hypertension. Because of these beneficial effects, activators of PPARs may have therapeutic potential in the prevention of cardiovascular disease beyond their actions on carbohydrate and lipid metabolism. The present chapter focuses on the role of PPARs in vascular biology and discusses the clinical implications of using PPAR agonists in the management of vascular disease.
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Vascular pharmacology · Jul 2006
ReviewEffects of PPAR gamma agonists on cardiovascular function in obese, non-diabetic patients.
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors, and when activated by their ligands, they induce perixosome proliferation. Three receptors have been identified: PPAR gamma, PPAR delta, and PPAR alpha, all with different tissue expression. PPAR gamma is predominantly expressed in adipose tissue and regulates the formation of fat cells and their function. ⋯ The impact of the thiazolidinediones on cardiovascular mortality is currently unclear but it appears that the thiazolidinediones exert numerous non-glycemic effects that may improve cardiovascular outcomes. Several non-TZD PPAR gamma agonists and combined PPAR gamma/alpha effect on cardiovascular disease are also being evaluated. These drugs have anti-inflammatory and vascular properties and are currently the subject of numerous studies targeting the primary and secondary prevention of macrovascular disease in patients with diabetes and insulin resistance and might be developed as anti-atherogenic agents on the basis of their actions.
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Vascular pharmacology · May 2006
Comparative StudyEffect of different ventilatory strategies on local and systemic cytokine production in intact swine lungs in vivo.
The purpose of the study was to investigate the effect of different ventilatory strategies on local and systemic cytokine production in swine with intact lungs in vivo after 4 h of mechanical ventilation. Twenty-five swine were anesthetized and then randomized into five groups (n = 5): (1) low tidal volume zero PEEP (LVZP); (2) medium tidal volume zero PEEP (MVZP); (3) high tidal volume zero PEEP (HVZP); (4) low tidal volume PEEP (LVP); (4) high tidal volume PEEP (HVP). Respiratory rate was adjusted to maintain normocapnia and fraction of inspired oxygen (FiO2) was 1.0. ⋯ There was a statistically significant increase in serum TNF-alpha levels at 4 h in LVP group compared to baseline and the other groups at 4 h. There was statistically significant increase in serum IL-10 levels in HVZP and LVP groups at 2 and 4 h which was significantly higher compared to the other groups at 4 h. Our results show that a) low volume MV may induce local and systemic pro- and anti-inflammatory cytokine increase b) in the presence of pro-inflammatory cytokine response there is also an anti-inflammatory response in the same compartment (lungs, circulation). c) There maybe loss of alveolar-to-systemic cytokine compartmentalization.