Intrarenal Anti-Leptin Treatment Attenuates Ischemia and Reperfusion Injury.

Introduction: Renal ischemia and reperfusion (IR) injury introduces cellular stress and is the main cause of acute kidney damage. Renal cells exposed to noxious stress induce the expression of the pleiotropic hormone leptin. As we have previously revealed a deleterious stress-related role for leptin expression, these results suggested that leptin is also involved in pathological renal remodeling.

Intraarterial anti-leptin therapy via ICA protects ipsilateral CA1 neurons subjected to ischemia and reperfusion.

Background: Brain reperfusion following an ischemic event is essential for tissue viability, however, it also involves processes that promote neuronal cell death. We have recently shown that local expression of the hormone leptin in cardiovascular organs drives deleterious remodeling. As cerebral ischemia-reperfusion (IR) lesions derive expression of both the leptin hormone and its receptor, we hypothesized that blocking leptin activity in the injured brain area will reduce the deleterious effects of IR injury.

Localized Antileptin Therapy Prevents Aortic Root Dilatation and Preserves Left Ventricular Systolic Function in a Murine Model of Marfan Syndrome.

Background Marfan syndrome (MFS) is a genetically transmitted connective tissue disorder characterized by aortic root dilatation, dissection, and rupture. Molecularly, MFS pathological features have been shown to be driven by increased angiotensin II in the aortic wall. Using an angiotensin II-driven aneurysm mouse model, we have recently demonstrated that local inhibition of leptin activity restricts aneurysm formation in the ascending and abdominal aorta.

Cardiac leptin overexpression in the context of acute MI and reperfusion potentiates myocardial remodeling and left ventricular dysfunction.

Background: Acute MI induces leptin expression in the heart, however the role of myocardial leptin in cardiac ischemia and reperfusion (IR) remains unknown. To shed light on the effects of elevated levels of leptin in the myocardium, we overexpressed cardiac leptin and assessed local remodeling and myocardial function in this context.

Methods And Results: Cardiac leptin overexpression was stimulated in mice undergoing IR by a single intraperitoneal injection of leptin antagonist (LepA).

Phase Ib Safety, Two-Dose Study of MultiGeneAngio in Patients with Chronic Critical Limb Ischemia.

Critical limb ischemia (CLI) is the most severe presentation of peripheral arterial disease. We developed cell-based therapy entailing intra-arterial injection of autologous venous endothelial cells (ECs) modified to express angiopoietin 1, combined with autologous venous smooth muscle cells (SMCs) modified to express vascular endothelial growth factor. This combination promoted arteriogenesis in animal models and was safe in patients with limiting claudication.

Local Application of Leptin Antagonist Attenuates Angiotensin II-Induced Ascending Aortic Aneurysm and Cardiac Remodeling.

Background: Ascending thoracic aortic aneurysm (ATAA) is driven by angiotensin II (AngII) and contributes to the development of left ventricular (LV) remodeling through aortoventricular coupling. We previously showed that locally available leptin augments AngII-induced abdominal aortic aneurysms in apolipoprotein E-deficient mice. We hypothesized that locally synthesized leptin mediates AngII-induced ATAA.

Phase I study of multi-gene cell therapy in patients with peripheral artery disease.

Unlabelled: Alternative treatment strategies for claudication are needed and cell-based therapies designed to induce angiogenesis are promising. The purpose of this report was to conduct a Phase I safety, dose-escalating, non-randomized, open-label study of autologous, fully differentiated venous endothelial and smooth muscle cells called MultiGeneAngio (MGA) for claudication due to peripheral artery disease. Twelve subjects, at two centers, received a single intra-arterial infusion of a suspension of equal amounts of transduced autologous venous smooth muscle cells expressing vascular endothelial growth factor (VEGF165) and endothelial cells expressing angiopoietin-1 (Ang-1) (Cohort 1: 1 × 10(7), Cohort 2: 2 × 10(7), Cohort 3: 5 × 10(7), Cohort 4: 7 × 10(7)).

Long-term renin-angiotensin blocking therapy in hypertensive patients with normal aorta may attenuate the formation of abdominal aortic aneurysms.

Renin-angiotensin system (RAS) has been implicated in the pathogenesis of abdominal aortic aneurysm (AAA). Angiotensin II type 1 receptor blocker (ARB), when given with angiotensin II prevents AAA formation in mice, but found ineffective in attenuating the progression of preexisting AAA. This study was designed to evaluate the effect of chronic RAS blockers on abdominal aortic diameter in hypertensive patients without known aortic aneurysm.

Endovascular repair of complex aortic aneurysms.

Background: Surgery for complex aortic aneurysms (thoracoabdominal, juxtarenal and pseudoaneurysms) is associated with a high morbidity and mortality rate. Branched and fenestrated stent grafts constitute a new technology intended as an alternative treatment for this disease.

Objectives: To describe a single-center experience with fenestrated and branched endografts for the treatment of complex aortic aneurysms.

Endovascular treatment of lower extremity ischemia in chronic renal failure patients on dialysis: early and intermediate term results.

Background: Peripheral arterial occlusive disease is common in patients with chronic renal failure requiring dialysis. Despite the increasing use of endovascular revascularization for lower extremity ischemia, the success rates of treating lower extremity ischemia in this challenging population remain obscure.

Objectives: To assess the results of endovascular revascularization for lower extremity ischemia in dialysis patients.

The deep femoral artery, a readily available inflow vessel for lower limb revascularization: a single-center experience.

The deep femoral artery (DFA) offers several advantages as an inflow vessel in lower-extremity bypasses. We report a single-center experience using the DFA as an inflow artery for lower-extremity revascularization. We reviewed all patients who underwent a lower-extremity bypass utilizing the DFA as the inflow vessel.

Leptin locally synthesized in carotid atherosclerotic plaques could be associated with lesion instability and cerebral emboli.

Background: Unstable carotid plaques cause cerebral emboli. Leptin promotes atherosclerosis and vessel wall remodeling. We hypothesized that carotid atherosclerotic lesion instability is associated with local leptin synthesis.

Locally applied leptin induces regional aortic wall degeneration preceding aneurysm formation in apolipoprotein E-deficient mice.

Objective: Leptin promotes atherosclerosis and vessel wall remodeling. As abdominal aortic aneurysm (AAA) formation involves tissue remodeling, we hypothesized that local leptin synthesis initiates and promotes this process.

Methods And Results: Human surgical AAA walls were analyzed for antigen and mRNA levels of leptin and leptin receptor, as well as mRNA for matrix metalloproteinases (MMP)-9 and MMP-12.

Murine ultrasound imaging for circumferential strain analyses in the angiotensin II abdominal aortic aneurysm model.

Objective: The underlying causes of abdominal aortic aneurysms (AAAs) remain obscure, although research tools such as the angiotensin II (Ang II) apolipoprotein E-deficient (apoE(-/-)) mouse model have aided investigations. Longitudinal imaging and determination of biomechanical forces in this small-scale model have been difficult. We hypothesized that high-frequency ultrasound biomicroscopy combined with speckle-tracking analytical strategies can be used to define the role of circumferential mechanical strain in AAA formation in the Ang II/apoE(-/-) mouse model of AAAs.

Clostridium septicum post-endovascular aneurysm repair stent-graft infection.

Endovascular aortic aneurysm repair (EVAR) is establishing its role as a valid alternative for the treatment of abdominal aortic aneurysm. Post-EVAR graft infection is a rare and devastating complication. The incidence of post-EVAR graft infection is yet to be defined, and available data at this stage consist of case reports and small series.

The vanishing giant abdominal aortic aneurysm.

Spontaneous sac size regression of a giant abdominal aortic aneurysm (AAA) is a rare event that has not been previously described. We report a case of an 89-year-old woman with a known 9-cm AAA, which was diagnosed in 2003. The patient had refused any kind of treatment at that time.

Endovascular management of mycotic aortic aneurysms.

Purpose: We report a single-center experience with the endovascular management of mycotic aortic aneurysms.

Case Reports: Four cases of mycotic aortic aneurysms are described; all treated with endovascular stent graft with variable configurations. All patients underwent successful placement of stent grafts for their aneurysms.

Leptin receptor is elevated in carotid plaques from neurologically symptomatic patients and positively correlated with augmented macrophage density.

Background: Carotid artery lesions from symptomatic patients are characterized by inflammation and neovascularization. The adipokine leptin promotes angiogenesis and activates inflammatory cells, and the leptin receptor (ob gene-encoded receptor), ObR, is expressed in advanced atherosclerotic lesions. The present study quantitatively analyzed ObR messenger RNA (mRNA) expression and immunoreactivity in carotid artery plaques from symptomatic and asymptomatic persons.

Expression of the leptin receptor in different types of vascular lesions.

Clinical and experimental evidence suggests that the adipokine leptin may be important for the development of cardiovascular complications associated with obesity, possibly through interaction with its receptor on vascular cells. In the present study, we systematically analysed expression of the leptin receptor in normal and diseased vascular specimens using immunohistochemistry, immunofluorescence and quantitative real time-PCR. In particular, human atherosclerotic plaques as well as experimental vascular lesions induced in hypercholesterolemic mice and minipigs, respectively, were examined.

Migraines linked to intrapulmonary right-to-left shunt.

Objective: To determine if there is an association between migraines and intrapulmonary right-to-left shunt.

Background: Several studies have described an association between migraines and intracardiac right-to-left shunt.

Methods: Patients with hereditary hemorrhagic telangiectasia (HHT) were retrospectively recruited from the Toronto Hereditary Hemorrhagic Telangiectasia Center Clinical Database.

[Endovascular repair of abdominal aortic aneurysms].

Abdominal aortic aneurysms (AAA) continue to be a major source of morbidity and mortality. The transfemoral placement of endoluminal stent-grafts for the treatment of AAAs, first described in 1991, offers a minimally invasive technique for the treatment of AAAs. The technology of endovascular repair of AAAs has progressed rapidly and the approach has proven to be safe and effective in the short- to mid-term.

Miniature self-contained intravascular magnetic resonance (IVMI) probe for clinical applications.

A miniature (1.73 mm in diameter) NMR probe, which contains a magnet and a radiofrequency (RF) coil, is presented. This probe is integrated at the tip of a standard catheter and can be inserted into the human coronary arteries, creating local magnetic fields needed to obtain the NMR signal from the blood vessel walls, without the need for external magnet or RF coils.

Diagnosis of thin-cap fibroatheromas by a self-contained intravascular magnetic resonance imaging probe in ex vivo human aortas and in situ coronary arteries.

Objectives: We sought to correlate findings obtained from a self-contained magnetic resonance imaging (MRI) probe with plaque morphology of ex vivo human aortas and coronary arteries.

Background: Early detection of thin-cap fibroatheromas (TCFAs) may allow for early preventive treatment of acute coronary syndromes. We developed an intravascular MRI catheter capable of imaging the arterial wall without external magnets or coils by differentiating lipid-rich and fibrotic-rich areas of the atherosclerotic plaque on the basis of differential water diffusion.