Transient central retina artery occlusion in patients undergone intravitreal anti-vascular endothelial growth factor injections

Purpose To evaluate the occurrence of transient central retinal artery occlusion following intravitreal anti-vascular endothelial growth factor injection. Methods Prospective, observational study of 807 patients (807 eyes) who were given intravitreal injections of ranibizumab or aflibercept to treat any cause of retinal vascular diseases between 1 January 2017 and 30 November 2018 at the Federal Fluminense University Hospital in Niteroi, and a private facility in Rio de Janeiro, Brazil. Patients who did not present transient central retinal artery occlusion were excluded. Results Among 4069 injections, only 18 patients (0.44%) presented transient central retinal artery occlusion, 14 mild cases (77.7%), and 4 severe cases (22.3%). The clinical factors associated with more severe cases of transient central retinal artery occlusion were the duration of the transient central retinal artery occlusion ( p = 0.001), number of prior injections ( p = 0.01), and a positive carotid Doppler test ( p = 0.01). Twelve cases (66.6%) had positive carotid artery obstruction (atheroma plaque size ≥70%) while 6 cases (33.3%) had negative carotid artery obstruction (atheroma plaque size <70%). The age group >60 years old ( p = 0.06), cup/disc ratio >0.6 ( p = 0.06), and pseudophakic lens status were also factors with association with transient central retinal artery occlusion, although did not meet criteria for statistical significance. The only patient who experienced a recurrent episode of transient central retinal artery occlusion had diabetic macular edema, positive carotid Doppler test, and cup/optic disc ratio >0.6. Conclusion Transient central retinal artery occlusion is a rare adverse event that can appear in patients with retinal vascular disease receiving anti-vascular endothelial growth factor therapy. The atheroma plaque size and the number of prior injections can be associated with the severity of the event.

Vascular Calcification: Key Roles of Phosphate and Pyrophosphate

Cardiovascular complications due to accelerated arterial stiffening and atherosclerosis are the leading cause of morbimortality in Western society. Both pathologies are frequently associated with vascular calcification. Pathologic calcification of cardiovascular structures, or vascular calcification, is associated with several diseases (for example, genetic diseases, diabetes, and chronic kidney disease) and is a common consequence of aging. Calcium phosphate deposition, mainly in the form of hydroxyapatite, is the hallmark of vascular calcification and can occur in the medial layer of arteries (medial calcification), in the atheroma plaque (intimal calcification), and cardiac valves (heart valve calcification). Although various mechanisms have been proposed for the pathogenesis of vascular calcification, our understanding of the pathogenesis of calcification is far from complete. However, in recent years, some risk factors have been identified, including high serum phosphorus concentration (hyperphosphatemia) and defective synthesis of pyrophosphate (pyrophosphate deficiency). The balance between phosphate and pyrophosphate, strictly controlled by several genes, plays a key role in vascular calcification. This review summarizes the current knowledge concerning phosphate and pyrophosphate homeostasis, focusing on the role of extracellular pyrophosphate metabolism in aortic smooth muscle cells and macrophages.

Network Protein Interaction in the link between Stroke and Periodontitis Interplay: A Pilot Bioinformatic Analysis

The clinical interaction between stroke and periodontitis has been consistently studied and confirmed. Hence, exploring potentially new protein interactions in this association using bioinformatic strategies presents potential interest. In this exploratory study, we conducted a protein–protein network interaction (PPI) search with documented encoded proteins for both stroke and periodontitis. Genes of interest were collected via GWAS database. The STRING database was used to predict the PPI networks, first in a sensitivity purpose (confidence cut-off of 0.7), and then with a highest confidence cut-off (0.9). Genes over-representation was inspected in the final network. As a result, we foresee a prospective protein network of interaction between stroke and periodontitis. Inflammation, pro-coagulant/pro-thrombotic state and, ultimately, atheroma plaque rupture is the main biological mechanism derived from the network. These pilot results may pave the way to future molecular and therapeutic studies to further comprehend the mechanisms between these two conditions.

Network Protein Interaction in the Link between Stroke and Periodontitis Interplay: A Pilot Bioinformatic Analysis

The clinical interaction between stroke and periodontitis has been consistently studied and confirmed. Hence, forecasting potentially new protein interactions in this association using bioinformatic strategies presents potential interest. In this exploratory study, we conducted a protein-protein network interaction (PPI) search with documented encoded proteins for both stroke and periodontitis. Genes of interest were collected via GWAS database. The STRING database was used to predict the PPI networks, first in a sensitivity purpose (confidence cut-off of 0.7), and then with a highest confidence cut-off (0.9). Genes over-representation was inspected in the final network. As a result, we foresee a prospective protein network of interaction between stroke and periodontitis. Inflammation, pro-coagulant/pro-thrombotic state and ultimately atheroma plaque rupture is the main biological mechanism derived from the network. These pilot results may pave the way to future molecular and therapeutic studies to further comprehend the mechanisms between these two conditions.

Post-Myocardial Infarction Ventricular Remodeling Biomarkers—The Key Link between Pathophysiology and Clinic

Studies in recent years have shown increased interest in developing new methods of evaluation, but also in limiting post infarction ventricular remodeling, hoping to improve ventricular function and the further evolution of the patient. This is the point where biomarkers have proven effective in early detection of remodeling phenomena. There are six main processes that promote the remodeling and each of them has specific biomarkers that can be used in predicting the evolution (myocardial necrosis, neurohormonal activation, inflammatory reaction, hypertrophy and fibrosis, apoptosis, mixed processes). Some of the biomarkers such as creatine kinase–myocardial band (CK-MB), troponin, and N-terminal-pro type B natriuretic peptide (NT-proBNP) were so convincing that they immediately found their place in the post infarction patient evaluation protocol. Others that are related to more complex processes such as inflammatory biomarkers, atheroma plaque destabilization biomarkers, and microRNA are still being studied, but the results so far are promising. This article aims to review the markers used so far, but also the existing data on new markers that could be considered, taking into consideration the most important studies that have been conducted so far.

Antioxidant Effects of PS5, a Peptidomimetic of Suppressor of Cytokine Signaling 1, in Experimental Atherosclerosis

The chronic activation of the Janus kinase/signal transducer and activator of the transcription (JAK/STAT) pathway is linked to oxidative stress, inflammation and cell proliferation. Suppressors of cytokine signaling (SOCS) proteins negatively regulate the JAK/STAT, and SOCS1 possesses a small kinase inhibitory region (KIR) involved in the inhibition of JAK kinases. Several studies showed that KIR-SOCS1 mimetics can be considered valuable therapeutics in several disorders (e.g., diabetes, neurological disorders and atherosclerosis). Herein, we investigated the antioxidant and atheroprotective effects of PS5, a peptidomimetic of KIR-SOCS1, both in vitro (vascular smooth muscle cells and macrophages) and in vivo (atherosclerosis mouse model) by analyzing gene expression, intracellular O2•− production and atheroma plaque progression and composition. PS5 was revealed to be able to attenuate NADPH oxidase (NOX1 and NOX4) and pro-inflammatory gene expression, to upregulate antioxidant genes and to reduce atheroma plaque size, lipid content and monocyte/macrophage accumulation. These findings confirm that KIR-SOCS1-based drugs could be excellent antioxidant agents to contrast atherosclerosis.

5-cis-, Trans- and Total Lycopene Plasma Concentrations Inversely Relate to Atherosclerotic Plaque Burden in Newly Diagnosed Type 2 Diabetes Subjects

Diabetic subjects are at increased risk of cardiovascular disease. Atherosclerosis, the common soil of most of the cardiovascular complications, is more prevalent and extensive in this population due not only to hyperglycemia, insulin resistance, and dyslipidemia, but also to inflammation and oxidative stress. Lycopenes are bioactive compounds with antioxidant and anti-inflammatory activities mostly supplied by tomato and tomato byproducts. We investigated the association between circulating lycopenes and carotid plaque burden in diabetic patients, in a cross-sectional study in 105 newly diagnosed diabetic subjects. Atheroma plaque (wall thickness ≥ 1.5 mm), number of plaques, and plaque burden (sum of maximum heights of all plaques) were assessed by sonographic evaluation of carotid arteries. Plasma lycopenes (5-cis-, 9-cis-, 13-cis-, and trans-lycopene) were quantified by high performance liquid chromatography–mass spectrometry HPLC-MS. Atheroma plaque was observed in 75 participants, from which 38 presented one plaque and 37 two or more carotid plaques. No differences were observed in the plasmatic concentrations of lycopenes between subjects with and without atherosclerotic plaque presence. However, plaque burden was inversely associated with 5-cis-lycopene, all cis-lycopene isomers, trans-lycopene, and total lycopene isomers (all, p < 0.05). High plasma levels of lycopenes inversely relate to atherosclerotic burden. We provide novel evidence that suggests that the consumption of compounds found in tomato and tomato byproducts might be beneficial for the prevention of atherosclerosis.

Isocaloric Walnut Inclusion in a Palm-Based High-Fat and High-Cholesterol Diet Stabilizes Advanced Atheroma Plaque in ApoE-Deficient Mice

Objectives The presence of lipid-rich, unstable atheroma plaques in the vascular tree is the harbinger of cardiovascular events. There is a low prevalence of unstable atheroma plaques in Mediterranean countries. This might explain in part the lower rates of cardiovascular disease in Southern Europe compared to Northern Europe and US. Consumption of certain foods paradigmatic of the Mediterranean Diet delays atherosclerosis progression. In a mouse model of accelerated atherosclerosis, we investigated whether the inclusion of walnuts within an atherogenic diet stabilizes advanced atheroma plaque. Methods Apolipoprotein E-deficient mice (male, 10-week old) were randomized to receive either regular chow (9.6% of energy as fat, n = 14); a palm oil-based high-fat diet (43% of energy as fat, n = 15); or an isocaloric high-fat diet in which palm oil was partially replaced by walnuts in a dose equivalent to 30 g/d in humans (n = 14). All diets contained 0.2% cholesterol. After 15 weeks of intervention, we evaluated changes in aortic atherosclerotic lesions (size and composition) and markers for inflammation, oxidative stress, necrosis and autophagy. Results There were no among-group differences in atherosclerotic size and extension, or oxidative stress. Compared to control diet, palm oil-diet induced plaque instability (higher lipid and necrosis, and lower collagen-to-lipid ratio). Walnut inclusion attenuated these features and decreased macrophage infiltration. Palm oil-based diet increased expression of chemokines, cytokines, inflammasome, and M1-macrophage marker compared to control diet. Such response was not observed in walnut group. Findings for walnut group could be explained by the differential aortic activation of NF-kB (down-regulated) and Nrf2 and autophagy (up-regulated). Conclusions Isocaloric inclusion of walnuts within an unhealthy high-fat diet stabilizes advanced atheroma plaque. This contributes novel mechanistic evidence for the cardiovascular benefits of sustained walnut consumption. Funding Sources Instituto de Salud Carlos III, Spain; Fondo de Investigación Sanitaria–Fondo Europeo de Desarrollo Regional, Spain. California Walnut Commission.