Atherosclerosis has long been known to be a chronic inflammatory disease. In addition, there is intense oxidative stress in atherosclerosis resulting from an imbalance between the excess reactive oxygen species (ROS) generation and inadequate anti-oxidant defense forces. The excess of the oxidative forces results in the conversion of low-density lipoproteins (LDL) to oxidized LDL (ox-LDL), which is highly atherogenic. The sub-endothelial deposition of ox-LDL, formation of foamy macrophages, vascular smooth muscle cell (VSMC) proliferation and migration, and deposition of collagen are central pathophysiologic steps in the formation of atherosclerotic plaque. Ox-LDL exerts its action through several different scavenger receptors, the most important of which is LOX-1 in atherogenesis. LOX-1 is a transmembrane glycoprotein that binds to and internalizes ox-LDL. This interaction results in variable downstream effects based on the cell type. In endothelial cells, there is an increased expression of cellular adhesion molecules, resulting in the increased attachment and migration of inflammatory cells to intima, followed by their differentiation into macrophages. There is also a worsening endothelial dysfunction due to the increased production of vasoconstrictors, increased ROS, and depletion of endothelial nitric oxide (NO). In the macrophages and VSMCs, ox-LDL causes further upregulation of the LOX-1 gene, modulation of calpains, macrophage migration, VSMC proliferation and foam cell formation. Soluble LOX-1 (sLOX-1), a fragment of the main LOX-1 molecule, is being investigated as a diagnostic marker because it has been shown to be present in increased quantities in patients with hypertension, diabetes, metabolic syndrome and coronary artery disease. LOX-1 gene deletion in mice and anti-LOX-1 therapy has been shown to decrease inflammation, oxidative stress and atherosclerosis. LOX-1 deletion also results in damage from ischemia, making LOX-1 a promising target of therapy for atherosclerosis and related disorders. In this article we focus on the different mechanisms for regulation, signaling and the various effects of LOX-1 in contributing to atherosclerosis.
29 April 2019 in Journal of Cardiovascular Pharmacology and Therapeutics
Background: Direct oral anticoagulants (DOACs) have been found to be similar or superior to warfarin in reducing ischemic stroke and intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF). We sought to examine the anticoagulation prescription patterns in community since the advent of DOACs and also evaluate the outcomes in terms of gastrointestinal (GI) bleeding, ischemic stroke, and ICH in real-world patients with AF receiving anticoagulation. Methods: This is a retrospective study comprising patients who were newly diagnosed with nonvalvular AF and were prescribed anticoagulants for stroke prevention. Prescription pattern of the anticoagulants based on CHA2DS2Vasc score was studied. Clinical outcomes of GI bleeding, ischemic stroke, and ICH were analyzed using a multivariate logistic regression model. Results: Of the 2362 patients with AF on anticoagulation, 44.7% were prescribed DOACs. Patients with CHA2DS2VASc score of ≥3 received a prescription for warfarin more often than DOACs ( P < .001). Multivariate logistic regression analysis revealed that the incidence of GI bleed (odds ratio [OR]: 0.91, 95% confidence interval [CI]: 0.62-1.35, P = .66) and stroke (OR: 0.77, 95% CI: 0.57-1.05, P = .10) was similar between warfarin and DOAC users. However, there was a trend toward lower ICH in the DOAC group (OR: 0.60, 95% CI: 0.36-1.01, P = .06). Conclusions: Prescription rate of DOACs for nonvalvular AF has increased significantly, with apixaban being the most commonly used agent. Patients with higher CHA2DS2-VASc score (≥3) are prescribed DOACs less often than warfarin. The reason for this discrepancy is unclear. Given the favorable risk–benefit profile of DOACs, further studies are needed to identify factors that determine anticoagulant selection in patients with AF with high thromboembolic risk.
8 March 2022 in Journal of Interventional Cardiac Electrophysiology
Atrial fibrillation (AF) is a common heart rhythm disorder that increases the risk of stroke and other cardiovascular complications. The Watchman FLX device is a percutaneous device used for the closure of the left atrial appendage in patients with atrial fibrillation and prevents blood clots from forming, thereby decreasing the risk of stroke. However, device dislodgement during the procedure can occur and compromise the effectiveness of the device. In this case report, we present the experience of an 86-year-old man with a history of atrial fibrillation, coronary artery disease, hypertension, and recent gastrointestinal bleeding due to diverticulosis. During the procedure, the device became dislodged prior to the planned release from the shaft due to the difficult anatomy of the appendage, which caused the operator to over-torque and kink the delivery sheath. The kinked sheath prevented the transmission of torque to the appropriate region of the sheath and caused the device to unscrew prematurely. Fortunately, the device was self-deployed in a satisfactory position, and no further intervention was required. The patient did not experience any complications prior to discharge and follow-up echocardiography showed proper positioning of the device. This case highlights the importance of careful technique during the Watchman FLX procedure and the need to replace the delivery sheath if kinking is noted to prevent unintentional dislodgement of the device. In addition, the case was written with the aid of the artificial intelligence-powered language model ChatGPT and demonstrates its benefits as well as calls for caution while using it for medical writing.
The SENTINEL Cerebral Protection System is one of the most commonly used devices for embolic protection during transcatheter aortic valve replacement. However, successful deployment of the SENTINEL device is often challenging in patients with a bovine aortic arch anatomy using the standard technique and requires extensive manipulation in the aortic arch increasing the risk of stroke. We describe a novel and simple technique of 2-filter deployment of SENTINEL device in patients with bovine arch anatomy. In this technique, after the deployment of the proximal filter, the device is hyperflexed on itself facing the lateral aspect of the ascending aorta instead of facing the descending aorta, with its tip pointing toward the common origin of the left common carotid artery (LCCA) and brachiocephalic trunk. The guidewire is then advanced to the LCCA. Since the guidewire can pass either anterior or posterior to the device shaft, the device needs to be untwisted either by clockwise or counterclockwise motion, before pulling the device shaft back to engage the LCCA, after which the distal filter can be deployed. Computed tomography scans obtained for planning transcatheter aortic valve replacement should be reviewed for the presence of bovine aortic arch anatomy so that this technique can be deployed directly, thereby reducing manipulations in the aortic arch, saving time, and not requiring additional equipment.