Abstract-CCAAT/enhancer-binding proteins (C/EBPs) upregulate transcription of various inflammatory cytokines and acute phase proteins, such as interleukin (IL)-1␤, IL-6, tumor necrosis factor-␣, and cyclooxygenase-2. Recent studies have demonstrated that peroxisome proliferator-activated receptor (PPAR)-␥ is present in atherosclerotic lesions, and negatively regulates expression of these genes. Interestingly, PPAR-␥ gene promoter has tandem repeats of C/EBP-binding motif, and C/EBP-␦ plays a pivotal role in transactivation of PPAR-␥ gene. It has been well known that the interaction between C/EBPs and PPAR-␥ plays a central role in maintaining adipocyte differentiation and glucometabolism; however, the relationship between PPAR-␥ and C/EBPs in the vessel wall remains unclear. In the present study, we showed that a high level of C/EBP-␦ expression induced by inflammation positively regulated transcription and protein expression of PPAR-␥ in vascular smooth muscle cells (VSMCs). On the other hand, PPAR-␥ ligands troglitazone, pioglitazone, and 15-deoxy-⌬ 12,14 -prostaglandin J 2 inhibited IL-1␤-induced IL-6 expression at a transcriptional revel in VSMCs. Functional promoter analysis revealed that PPAR-␥ ligands inhibited IL-1␤-induced transactivation of IL-6 gene via suppression of not only nuclear factor-B but also C/EBP-DNA binding. Moreover, PPAR-␥ ligands suppressed protein expression and transcription of C/EBP-␦ through dephosphorylation of signal transducer and activator of transcription 3. These findings strongly suggest that C/EBP-␦ is negatively autoregulated via transactivation of PPAR-␥. This feedback mechanism probably downregulates transcription of inflammatory cytokines and acute phase proteins, and modulates inflammatory responses in the early process of atherosclerosis.

No abstract

No abstract

Abstract-To elucidate the relationship between postprandial hypotension (PPH) and asymptomatic cerebrovascular damage, we evaluated changes in blood pressure after a meal by 24-hour blood pressure monitoring in 70 hospitalized essential hypertensive patients aged Ն50 years. They received a diet containing standard nutritional ingredients with 120 mmol (7 g) NaCl and were free from medication for at least 1 week. PPH was defined as the mean reduction of systolic blood pressure during 2 hours after a meal. Patients were divided into three groups according to mean values of PPH after 3 meals: PPH-1 (nϭ16, 5 mm HgՅPPHϽ10 mm Hg), PPH-2 (nϭ18, PPHՆ10 mm Hg), and normal (nϭ36, PPHϽ5 mm Hg). As asymptomatic cerebrovascular damage, lacunae and leukoaraiosis were evaluated by magnetic resonance imaging. PPH did not correlate with daytime or nighttime blood pressure or the nondipper phenomenon; however, PPH was significantly related to asymptomatic cerebrovascular damage. The prevalence of lacunae in the normal, PPH-1, and PPH-2 groups was 44%, 69%, and 83%, respectively ( 2 ϭ8.22, PϽ0.05). The number of lacunae in the normal, PPH-1, and PPH-2 groups was 1.0Ϯ1.3, 1.3Ϯ1.2, and 1.9Ϯ1.4, respectively (F[2,67]ϭ3.2, PϽ0.05). The prevalence of advanced leukoaraiosis in the normal, PPH-1, and PPH-2 groups was 44%, 50%, and 83%, respectively ( 2 ϭ7.63, PϽ0.05). Severity score of leukoaraiosis in the normal, PPH-1, and PPH-2 groups was 1.5Ϯ0.7, 1.7Ϯ0.8, and 2.1Ϯ0.7, respectively (F [2,67] has been shown to be related to several clinical abnormalities, including advanced end-organ damage, 1-3 secondary hypertension, 4 and autonomic nervous system dysfunction. 5 Several studies have demonstrated a linkage between asymptomatic brain damage and alteration of the diurnal change in BP. 2,6 -8 Recently, it has also been shown that dysregulation of postural change in BP is associated with advanced silent cerebrovascular damage in hypertension in the elderly. 9 Asymptomatic cerebrovascular damage, often found in elderly hypertensive individuals, is associated with cognitive dysfunction, 9 depression of mood, 10 and reduced capacity of the cerebral circulation. 11,12 It has also been shown that patients with asymptomatic lacunae have a significantly higher incidence of future stroke than normal subjects. 13 Postprandial hypotension (PPH) is a relatively common phenomenon frequently observed in elderly hypertensive patients. 14 However, only a few studies have investigated the effect of PPH on the diurnal change in BP in hypertensive patients. 15,16 In our previous study, 16 we evaluated PPH with ambulatory BP monitoring (ABPM) and showed that PPH contributed to the variability of BP in the daytime and the morning surge of BP, independent of the dipper and nondipper phenomena. Clinically, PPH can cause light-headedness, fainting, falls, or even transient ischemic attack. 14 Recently, it has also been shown that PPH is an independent risk factor for future mortality, coronary events, and stroke. 17 These findings suggest the relevance of PPH ...