Angioplasty, Balloon ; methods ; Atherosclerosis ; pathology ; therapy ; Humans ; Hypertension ; complications ; drug therapy ; Renal Artery Obstruction ; etiology ; therapy ; Stents

The nuclear hormone receptor PPARgamma is activated by several agonists, including members of the thiazolidinedione group of insulin sensitizers. Pleiotropic beneficial effects of these agonists, independent of their blood glucose-lowering effects, have recently been demonstrated in the vasculature. PPARgamma agonists have been shown to lower blood pressure in animals and humans, perhaps by suppressing the renin-angiotensin (Ang)-aldosterone system (RAAS), including the inhibition of Ang II type 1 receptor expression, Ang-II-mediated signaling pathways, and Ang-II-induced adrenal aldosterone synthesis/secretion. PPARgamma agonists also inhibit the progression of atherosclerosis in animals and humans, possibly through a pathway involving the suppression of RAAS and the thromboxane A2 system, as well as the protection of endothelial function. Moreover, PPARgamma-agonist-mediated renal protection, especially the reduction of albuminuria, has been observed in diabetic nephropathy, including animal models of the disease, and in non-diabetic renal dysfunction. The renal protective activities may reflect, at least in part, the ability of PPARgamma agonists to lower blood pressure, protect endothelial function, and cause vasodilation of the glomerular efferent arterioles. Additionally, anti-neoplastic effects of PPARgamma agonists have recently been described. Based on the multiple therapeutic actions of PPARgamma agonists, they will no doubt lead to novel approaches in the treatment of lifestyle-related and other diseases.
Animals ; Atherosclerosis/prevention & control ; Humans ; Hypertension/drug therapy ; Hypoglycemic Agents/*pharmacology ; Kidney Diseases/etiology ; PPAR gamma/*agonists ; PPAR-beta/agonists

Atherosclerosis ; blood ; drug therapy ; etiology ; C-Reactive Protein ; analysis ; Humans ; Lipoproteins, LDL ; blood ; PPAR gamma ; agonists ; Vasculitis ; complications

BACKGROUNDIncreased risk of atherosclerosis has been reported in patients with human immunodeficiency virus (HIV) infection since highly active antiretroviral therapy (HAART) has come into use. However, there is no clear evidence of premature atherosclerosis in Chinese HIV-infected patients. Our study was designed to determine the relationship between HIV infection and atherosclerosis in Chinese HIV-infected patients.

METHODSOne hundred and forty-five patients were enrolled in this study. These included 82 HIV-infected patients (41 HAART-treated and 41 antiretroviral therapy (ART) naïve patients) and 43 HIV-negative control subjects. Data on traditional cardiovascular risk factors, HIV infection parameters, and treatment regimens were collected. Pulse wave velocity (PWV) was determined using a pulse pressure analyzer to evaluate the function of the arterial wall as an indicator of atherosclerotic vascular damage.

RESULTSA higher PWV ((1358.3 ± 117.8) cm/s vs. (1270.2 ± 189.2) cm/s, P = 0.010) was found in ART naïve HIV-infected patients compared with control subjects. However, HAART treated patients had lower PWV compared to ART naïve patients ((1283.8 ± 181.4) cm/s vs. (1358.0 ± 117.8) cm/s, P = 0.033). Multiple regression analysis revealed that age (B = 5.218, 95% confidence interval (CI) 1.420 - 9.016, P = 0.008), current smoking (B = -74.671, 95%CI -147.003 to -2.339, P = 0.043) and HAART (92.7% patients on a protease inhibitor-free regimen) (B = -169.169, 95%CI -272.508 to -65.831, P = 0.010) were associated with reduced PWV in HIV-infected patients.

CONCLUSIONSReduced PWV in HIV-infected Chinese patients indicates that they are more likely to develop arterial wall stiffness, possibly by atherosclerosis. A protease inhibitor-free regime may be protective for arterial wall of HIV infected patients.

Acquired Immunodeficiency Syndrome ; complications ; drug therapy ; physiopathology ; Adult ; Antiretroviral Therapy, Highly Active ; Atherosclerosis ; etiology ; Female ; Humans ; Male ; Middle Aged ; Pulsatile Flow ; Regression Analysis ; Vascular Stiffness

Aged ; Angiography ; Angioplasty, Balloon ; methods ; Atherosclerosis ; complications ; Drug-Eluting Stents ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Renal Artery Obstruction ; diagnostic imaging ; etiology ; therapy ; Treatment Outcome ; Ultrasonography

Adolescent ; Atherosclerosis ; drug therapy ; etiology ; prevention & control ; therapy ; Child ; Humans ; Hyperlipidemias ; complications ; prevention & control ; therapy ; Hypolipidemic Agents ; therapeutic use ; Life Style ; Obesity ; complications ; prevention & control ; Primary Prevention ; Risk Factors

AIMTo evaluate whether the response to sildenafil administration in patients with arterial erectile dysfunction (ED) was related to their peak systolic velocity (PSV), peripheral atherosclerosis, cardiovascular risk factors (RF) and/or comorbidities at low cardiovascular risk.

METHODSWe enrolled 97 patients with 1-2 RF and comorbidities, combined with arterial ED alone (group A, n = 27), ED plus atherosclerotic carotid artery (group B, n = 23), ED plus lower limb artery abnormalities (group C, n = 25), and ED plus carotid and lower limb artery abnormalities (group D, n = 22). Sildenafil efficacy (100 mg twice a week for 12 weeks) was also examined in patients with =or>3 RF, peripheral atherosclerosis and no cardiovascular comorbidities (group E, n = 20).

RESULTSMedian PSV was 24.1, 21.0, 19.3, 14.5 and 17.5 cm/s in groups A, B, C, D and E, respectively. Sildenafil response was higher in group A patients (77.8%), intermediate in groups B and C (65.2% and 56%) and lowest in groups D (45.4%) and E (50%), and the response in latter two groups was significantly lower than in the other three groups. In addition, sildenafil response was negatively influenced by: =or>3 RF, peripheral atherosclerosis and no systemic comorbidity, or presence of 1-2 RF associated with extended atherosclerosis and comorbidities. The number of comorbidities was positively related to atherosclerosis localization or extension (25, 35, 38 and 47 in groups A, B, C and D, respectively).

CONCLUSIONLow sildenafil efficacy in patients with arterial ED was associated with extended atherosclerosis. These patients should undergo extensive ultrasonography and a full cardiovascular examination.

Aged ; Arterial Occlusive Diseases ; complications ; drug therapy ; physiopathology ; Atherosclerosis ; complications ; Cardiovascular Diseases ; complications ; drug therapy ; Erectile Dysfunction ; drug therapy ; etiology ; physiopathology ; Humans ; Lower Extremity ; blood supply ; Male ; Middle Aged ; Physical Examination ; Piperazines ; therapeutic use ; Purines ; therapeutic use ; Regional Blood Flow ; physiology ; Retrospective Studies ; Risk Factors ; Sildenafil Citrate ; Sulfones ; therapeutic use ; Treatment Outcome ; Vasodilator Agents ; therapeutic use

Chemokines and chemokine receptors play a role in migration of circulating leukocytes to the region of inflammation. Human LZIP is an uncharacterized transcription factor and is known to participate in leukotactin (Lkn)-1/CCL15-induced cell migration. We investigated the role of human LZIP in expression of CC chemokine receptors (CCRs) and its involvement in monocyte migration. RNase protection analysis showed that LZIP increased mRNA expression of CCR2 and CCR1 in THP-1 cells. Surface expressions of both CCR2 and CCR1 were also increased by LZIP. Results from an electrophoretic mobility shift assay showed that LZIP binds to the C/EBP element in the CCR2 promoter. LZIP also enhanced the chemotactic activities of monocyte chemoattractant protein-1/CCL2 and Lkn-1. These results suggest that LZIP regulates expression of chemokine receptors that are involved in monocyte migration.
Atherosclerosis/drug therapy/etiology ; CCAAT-Enhancer-Binding Proteins/genetics/immunology/*metabolism ; Cell Line, Tumor ; Cell Movement/drug effects/*physiology ; Chemokine CCL2/*pharmacology ; Chemokines, CC/pharmacology ; Cyclic AMP Response Element-Binding ; Humans ; Macrophage Inflammatory Proteins/pharmacology ; Monocytes/drug effects/metabolism ; Promoter Regions, Genetic ; Protein Binding ; RNA, Messenger/analysis ; Receptors, CCR1/biosynthesis/genetics ; Receptors, CCR2/*biosynthesis/genetics ; Transcriptional Activation/drug effects ; Transfection ; Transgenes