optical-coherence-tomography-based-biomechanical-fluid-structure

Optical Coherence Tomography Based Biomechanical Fluid-Structure Interaction Analysis of Coronary Atherosclerosis Progression

In this paper, we present a complete workflow for the biomechanical analysis of atherosclerotic plaque in the coronary vasculature. With atherosclerosis ...

South Australian Health and Medical Research Institute (SAHMRI)

INACTIVE - University of Adelaide

Central Adelaide Local Health Network

Incidence and characterisation of spontaneous coronary artery dissection as a cause of acute coronary syndrome--A single-centre Australian experience.

Management of acute coronary syndrome in the very elderly.

The pathogenesis of cardiomyopathy and heart failure (HF) is underpinned by complex changes at subcellular, cellular and extracellular levels in the ventricular myocardium. For all of the gains that conventional treatments for HF have brought to mortality and morbidity, they do not adequately address the loss of cardiomyocyte numbers in the remodeling ventricle. Originally conceived to address this problem, cellular transplantation for HF has already gone through several stages of evolution over the past two decades. Various cell types and delivery routes have been implemented to positive effect in preclinical models of ischemic and nonischemic cardiomyopathy, with pleiotropic benefits observed in terms of myocardial remodeling, systolic and diastolic performance, perfusion, fibrosis, inflammation, metabolism and electrophysiology. To a large extent, these salubrious effects are now attributed to the indirect, paracrine capacity of transplanted stem cells to facilitate endogenous cardiac repair processes. Promising results have also followed in early phase human studies, although these have been relatively modest and somewhat inconsistent. This review details the preclinical and clinical evidence currently available regarding the use of pluripotent stem cells and adult-derived progenitor cells for cardiomyopathy and HF. It outlines the important lessons that have been learned to this point in time, and balances the promise of this exciting field against the key challenges and questions that still need to be addressed at all levels of research, to ensure that cell therapy realizes its full potential by adding to the armamentarium of HF management. 

Cellular Therapy for Heart Failure.

Vitamin D and Cardiovascular Disease.

Nitric oxide (NO) is a key regulator of endothelial cell and vascular function. The direct measurement of NO is challenging due to its short half-life, and as such surrogate measurements are typically used to approximate its relative concentrations. Here we demonstrate that ruthenium-based [Ru(bpy)(dabpy)] is a potent sensor for NO in its irreversible, NO-bound active form, [Ru(bpy)(T-bpy)]. Using spectrophotometry we established the sensor's ability to detect and measure soluble NO in a concentration-dependent manner in cell-free media. Endothelial cells cultured with acetylcholine or hydrogen peroxide to induce endogenous NO production showed modest increases of 7.3 ± 7.1% and 36.3 ± 25.0% respectively in fluorescence signal from baseline state, while addition of exogenous NO increased their fluorescence by 5.2-fold. The changes in fluorescence signal were proportionate and comparable against conventional NO assays. Rabbit blood samples immediately exposed to [Ru(bpy)(dabpy)] displayed 8-fold higher mean fluorescence, relative to blood without sensor. Approximately 14% of the observed signal was NO/NO adduct-specific. Optimal readings were obtained when sensor was added to freshly collected blood, remaining stable during subsequent freeze-thaw cycles. Clinical studies are now required to test the utility of [Ru(bpy)(dabpy)] as a sensor to detect changes in NO from human blood samples in cardiovascular health and disease.

A Novel Ruthenium-based Molecular Sensor to Detect Endothelial Nitric Oxide.

The cellular origins of vasa vasorum are ill-defined and may involve circulating or local progenitor cells. We previously discovered that murine aortic adventitia contains Sca-1CD45 progenitors that produce macrophages. Here we investigated whether they are also vasculogenic. In aortas of C57BL/6 mice, Sca-1CD45 cells were localised to adventitia and lacked surface expression of endothelial markers (<1% for CD31, CD144, TIE-2). In contrast, they did show expression of CD31, CD144, TIE-2 and VEGFR2 in atherosclerotic ApoE aortas. Although Sca-1CD45 cells from C57BL/6 aorta did not express CD31, they formed CD31 colonies in endothelial differentiation media and produced interconnecting vascular-like cords in Matrigel that contained both endothelial cells and a small population of macrophages, which were located at branch points. Transfer of aortic Sca-1CD45 cells generated endothelial cells and neovessels de novo in a hindlimb model of ischaemia and resulted in a 50% increase in perfusion compared to cell-free control. Similarly, their injection into the carotid adventitia of ApoE mice produced donor-derived adventitial and peri-adventitial microvessels after atherogenic diet, suggestive of newly formed vasa vasorum. These findings show that beyond its content of macrophage progenitors, adventitial Sca-1CD45 cells are also vasculogenic and may be a source of vasa vasorum during atherogenesis.

Vasculogenic properties of adventitial Sca-1CD45 progenitor cells in mice: a potential source of vasa vasorum in atherosclerosis.

Coronary Vasospasm Induced by Phentermine.

Spontaneous coronary artery dissection (SCAD) is an uncommon, non-iatrogenic, non-atherosclerotic cause of acute coronary syndrome. A lack of large prospective cohort studies and randomised controlled trials means that important questions about clinical characteristics and outcomes of patients with SCAD are yet to be fully answered.

Systematic review and meta-analysis of the clinical characteristics and outcomes of spontanous coronary artery dissection.

Atherosclerotic coronary artery disease has a complex pathogenesis which extends beyond cholesterol intimal infiltration. It involves chronic inflammation of the coronary artery wall driven by systemic and local activation of both the adaptive and innate immune systems, which can ultimately result in the rupture or erosion of atherosclerotic plaque, leading to thrombosis and myocardial infarction (MI). Despite current best practice care, including the widespread use of cholesterol-lowering statins, atherothrombotic cardiovascular events recur at alarming rates post-MI. To a large extent, this reflects residual inflammation that is not adequately controlled by contemporary treatment. Consequently, there has been increasing interest in the pharmacological targeting of inflammation to improve outcomes in atherosclerotic cardiovascular disease. This has comprised both novel pathway-specific agents, most notably the anti-interleukin-1 beta monoclonal antibody, canakinumab, and the repurposing of established, broad-acting drugs, such as colchicine, that are already approved for the management of other inflammatory conditions. Here we discuss the importance of inflammation in mediating atherosclerosis and its complications and provide a timely update on "new" and "old" anti-inflammatory therapies currently being investigated to target it.

Inflammation in Coronary Atherosclerosis and Its Therapeutic Implications.

The majority of coronary atherothrombotic events presenting as myocardial infarction (MI) occur as a result of plaque rupture or erosion. Understanding the evolution from a stable plaque into a life-threatening, high-risk plaque is required for advancing clinical approaches to predict atherothrombotic events, and better treat coronary atherosclerosis. Unfortunately, none of the coronary imaging approaches used in clinical practice can reliably predict which plaques will cause an MI. Currently used imaging techniques mostly identify morphological features of plaques, but are not capable of detecting essential molecular characteristics known to be important drivers of future risk. To address this challenge, engineers, scientists, and clinicians have been working hand-in-hand to advance a variety of multimodality intravascular imaging techniques, whereby 2 or more complementary modalities are integrated into the same imaging catheter. Some of these have already been tested in early clinical studies, with other next-generation techniques also in development. This review examines these emerging hybrid intracoronary imaging techniques and discusses their strengths, limitations, and potential for clinical translation from both an engineering and clinical perspective.

Article	Year
Incidence and characterisation of spontaneous coronary artery dissection as a cause of acute coronary syndrome--A single-centre Australian experience. International journal of cardiology\| PubMed ID: 26426273	2016
Management of acute coronary syndrome in the very elderly. Lancet (London, England)\| PubMed ID: 26794723	2016
Cellular Therapy for Heart Failure. Current cardiology reviews\| PubMed ID: 27280304	2016
Vitamin D and Cardiovascular Disease. Heart, lung & circulation\| PubMed ID: 30047471	2018
A Novel Ruthenium-based Molecular Sensor to Detect Endothelial Nitric Oxide. Scientific reports\| PubMed ID: 30737439	2019
Vasculogenic properties of adventitial Sca-1CD45 progenitor cells in mice: a potential source of vasa vasorum in atherosclerosis. Scientific reports\| PubMed ID: 31086203	2019
Coronary Vasospasm Induced by Phentermine. Mayo Clinic proceedings\| PubMed ID: 31272562	2019
Systematic review and meta-analysis of the clinical characteristics and outcomes of spontanous coronary artery dissection. International journal of cardiology\| PubMed ID: 32861717	2021
Inflammation in Coronary Atherosclerosis and Its Therapeutic Implications. Cardiovascular drugs and therapy\| PubMed ID: 33170943	2020
Multimodality Intravascular Imaging of High-Risk Coronary Plaque. JACC. Cardiovascular imaging\| PubMed ID: 34023267	2022

Peter J. Psaltis

Biography

JoVE Journal Publications

Other Publications