Crosstalk between cells in the blood vessel wall is vital to normal vascular function and is perturbed in diseases such as atherosclerosis and hypertension. Perivascular adipocytes reside at the adventitial border of blood vessels but until recently were virtually ignored in studies of vascular function. However, perivascular adipocytes have been demonstrated to be powerful endocrine cells capable of responding to metabolic cues and transducing signals to adjacent blood vessels. Accordingly, crosstalk between perivascular adipose tissue (PVAT) and blood vessels is now being intensely examined. Emerging evidence suggests that PVAT regulates vascular function through numerous mechanisms, but evidence to date suggests modulation of three key aspects that are the focus of this review: inflammation, vasoreactivity, and smooth muscle cell proliferation. Characteristics of Perivascular AdipocytesTo begin to understand how PVAT potentially regulates vascular function, it is necessary to review the characteristics of this adipose depot. First, perivascular adipocytes are not separated from the blood vessel wall by a fascial layer or elastic lamina and actually encroach into the outer adventitial region [1,2]. The absence of an anatomic barrier suggests that mediators secreted by perivascular adipocytes can readily gain access into the blood vessel wall. Also, interspersed within the PVAT is the vasa vasorum, which proliferates during vascular inflammation and injury [3][4][5] and may transmit mediators released by PVAT to the inner vasculature. Second, perivascular adipocytes are morphologically and functionally distinct from adipocytes of other regional adipose depots, which likely have a direct bearing on vascular cell crosstalk [1,6] Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Role of PVAT in Inflammatory CrosstalkSecretion of mediators that regulate inflammation is a characteristic feature of adipocytes. These mediators can be divided into two broad, interacting categories: adipokines and cytokines (summarized in Table). Within both categories, individual mediators can be classified as pro-or anti-inflammatory, although the distinction is often blurred. A primary function of pro-inflammatory cytokines is to recruit inflammatory cells, which are also capable of secreting cytokines and certain adipokines. Moreover, crosstalk between inflammatory cells and adipocytes plays a critical role in regulating adipose depot functions.Leptin was one of the first adipokines to be discovered and has been shown to function primarily as a pro-inflammatory mediat...

Differentiation of preadipocytes into mature adipocytes capable of efficiently storing lipids is an important regulatory mechanism in obesity. Here, we examined the involvement of histone deacetylases (HDACs) and histone acetyltransferases (HATs) in the regulation of adipogenesis. We find that among the various members of the HDAC and HAT families, only HDAC9 exhibited dramatic down-regulation preceding adipogenic differentiation. Preadipocytes from HDAC9 gene knock-out mice exhibited accelerated adipogenic differentiation, whereas HDAC9 overexpression in 3T3-L1 preadipocytes suppressed adipogenic differentiation, demonstrating its direct role as a negative regulator of adipogenesis. HDAC9 expression was higher in visceral as compared with subcutaneous preadipocytes, negatively correlating with their potential to undergo adipogenic differentiation in vitro. HDAC9 localized in the nucleus, and its negative regulation of adipogenesis segregates with the N-terminal nuclear targeting domain, whereas the C-terminal deacetylase domain is dispensable for this function. HDAC9 co-precipitates with USF1 and is recruited with USF1 at the E-box region of the C/EBP␣ gene promoter in preadipocytes. Upon induction of adipogenic differentiation, HDAC9 is down-regulated, leading to its dissociation from the USF1 complex, whereas p300 HAT is up-regulated to allow its association with USF1 and accumulation at the E-box site of the C/EBP␣ promoter in differentiated adipocytes. This reciprocal regulation of HDAC9 and p300 HAT in the USF1 complex is associated with increased C/EBP␣ expression, a master regulator of adipogenic differentiation. These findings provide new insights into mechanisms of adipogenic differentiation and document a critical regulatory role for HDAC9 in adipogenic differentiation through a deacetylase-independent mechanism.

Background:A growing body of evidence suggests that the presence of a right bundle branch block (RBBB) is a negative prognostic indicator in patients with and without preexisting heart disease. Even though electromechanical activation of the right ventricle (RV) in patients with RBBB and pulmonary hypertension (PH) has been investigated; a direct comparison of the presence of RBBB, on the duration of RV mechanical systole using echocardiography has not been studied.Materials and Methods:In this retrospective study, we analyzed the echocardiograms of 40 patients by measuring the magnitude and timing of tricuspid annulus plane systolic excursion (TAPSE) and tricuspid annulus systolic velocity (TA S’). Patients were selected to form four groups of ten patients based on the presence or absence of RBBB and PH to determine if RBBB has any effect on the time-to-peak of TAPSE or TA S’, which for our purposes serves as a measure of duration of RV mechanical systole.Results:Our results demonstrate that RBBB leads to a measurable prolongation of TAPSE and TA S’ in patients without PH. Time-to-peak of TAPSE or TA S’ was not significantly prolonged in patients with PH.Conclusions:The results of this pilot study show that RV mechanical systole is prolonged in patients with RBBB, and the addition of PH attenuates this change. Additional prospective studies are now required to elucidate further the electrical and mechanical dyssynchrony that occurs as a result of RBBB, and how these new echocardiographic measurements can be applied clinically to risk stratify patients with RBBB and PH.

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