Increased endothelin-1-mediated vasoconstrictor tone in human obesity: effects of gut hormones.

The heavy impact of obesity on the development and progression of cardiovascular disease has sparked sustained efforts to uncover the mechanisms linking excess adiposity to vascular dysfunction. Impaired vasodilator reactivity has been recognized as an early hemodynamic abnormality in obese patients, but also increased vasoconstrictor tone importantly contributes to their vascular damage. In particular, upregulation of the endothelin (ET)-1 system, consistently reported in these patients, might accelerate atherosclerosis and its complication, given the pro-inflammatory and mitogenic properties of ET-1. In recent years, a number of gut hormones, in addition to their role as modulators of food intake, energy balance, glucose and lipid metabolism, and insulin secretion and action, have demonstrated favorable vascular actions. They increase the bioavailability of vasodilator mediators like nitric oxide, but they have also been shown to inhibit the ET-1 system. These features make gut hormones promising tools for targeting both the metabolic and cardiovascular complications of obesity, a view supported by recent large-scale clinical trials indicating that novel drugs for type 2 diabetes with cardiovascular potential may translate into clinically significant advantages. Therefore, there is real hope that better understanding of the properties of gut-derived substances might provide more effective therapies for the obesity-related cardiometabolic syndrome.

Vascular hyperpolarization in human physiology and cardiovascular risk conditions and disease.

Hyperpolarization causing smooth muscle relaxation contributes to the maintenance of vascular homeostasis, particularly in small-calibre arteries and arterioles. It may also become a compensatory vasodilator mechanism upregulated in states with impaired nitric oxide (NO) availability. Bioassay of vascular hyperpolarization in the human circulation has been hampered by the complexity of mechanisms involved and the limited availability of investigational tools. Firm evidence, however, supports the notion that hyperpolarization participates in the regulation of resting vasodilator tone and vascular reactivity in healthy subjects. In addition, an enhanced endothelium-derived hyperpolarization contributes to both resting and agonist-stimulated vasodilation in a variety of cardiovascular risk conditions and disease. Thus, hyperpolarization mediated by epoxyeicosatrienoic acids (EETs) and H2 O2 has been observed in coronary arterioles of patients with coronary artery disease. Similarly, ouabain-sensitive and EETs-mediated hyperpolarization has been observed to compensate for NO deficiency in patients with essential hypertension. Moreover, in non-hypertensive patients with multiple cardiovascular risk factors and in hypercholesterolaemia, KCa channel-mediated vasodilation appears to be activated. A novel paradigm establishes that perivascular adipose tissue (PVAT) is an additional regulator of vascular tone/function and endothelium is not the only agent in vascular hyperpolarization. Indeed, some PVAT-derived relaxing substances, such as adiponectin and angiotensin 1-7, may exert anticontractile and vasodilator actions by the opening of KCa channels in smooth muscle cells. Conversely, PVAT-derived factors impair coronary vasodilation via differential inhibition of some K+ channels. In view of adipose tissue abnormalities occurring in human obesity, changes in PVAT-dependent hyperpolarization may be relevant for vascular dysfunction also in this condition.

Carotid free-floating thrombus in woman with meningioma: a case report and review of the literature.

OBJECTIVE: Several reports have previously described the coexistence of severe carotid artery disorders and brain tumors, in particular meningioma, mainly consisting of arterial occlusion or obstruction due to direct compression by tumor mass, with possible presence of transient neurological symptoms as well as complete cerebral infarction. Free-floating thrombus (FFT) is an uncommon condition, characterized by the presence of thrombotic material partially attached to the arterial wall with evidence of heartbeat associated floating. To our knowledge, our case represents the first report in literature about presence of internal carotid FFT in patient affected by meningioma. CASE REPORT: In this report, sharing singular images and videos of this uncommon condition, we present the first case of a right internal carotid artery FFT in a 59-year-old woman affected by meningioma, successfully treated with antiplatelet medication together with anticoagulation and high dose of statins. CONCLUSIONS: Our case confirms the possible association between carotid artery disorders and meningioma, involving for the first time a FFT. These findings make desirable to explore carotid district in patients with brain tumors, especially meningioma, even if symptoms suggestive of ischemic suffering are not present, in order to make an early diagnosis, so preventing marked ischemic events.

Tumor necrosis factor-alpha antagonism improves endothelial dysfunction in patients with Crohn's disease.

This study assessed the presence of endothelial dysfunction in patients with inflammatory bowel diseases (IBDs) and evaluated the possible role of tumor necrosis factor (TNF)-alpha in the pathophysiology of this abnormality. Similar elevations in circulating markers of inflammation (C-reactive protein and interleukin-6) were observed in Crohn's disease and ulcerative colitis compared to controls. Endothelium-dependent vasodilation to acetylcholine was impaired in Crohn's disease, but not in ulcerative colitis. Endothelium-independent vasodilation to sodium nitroprusside, by contrast, was not different among the three groups. The TNF-alpha neutralizing antibody, infliximab, enhanced the responsiveness to acetylcholine, but not to nitroprusside, in Crohn's disease, without modifying vascular responses to both drugs in ulcerative colitis. In conclusion, despite comparable degrees of systemic inflammation in the two IBDs, endothelial dysfunction is a selective feature of Crohn's disease and is beneficially affected by intravascular TNF-alpha neutralization. These findings underscore the role of selective cytokine targeting in improving endothelial function in patients with Crohn's disease.