Pectins from various sources inhibit galectin-3-related cardiac fibrosis

Purpose of the study: A major challenge in cardiology remains in finding a therapy for cardiac fibrosis. Inhibition of galectin-3 with pectins attenuates fibrosis in animal models of heart failure. The purpose of this study is to identify pectins with the strongest galectin-3 inhibitory capacity. We evaluated the in vitro inhibitory capacity, identified potent pectins, and tested if this potency could be validated in a mouse model of myocardial fibrosis. Methods: Various pectin fractions were screened in vitro. Modified rhubarb pectin (EMRP) was identified as the most potent inhibitor of galectin-3 and compared to the well-known modified citrus pectin (MCP). Our findings were validated in a mouse model of myocardial fibrosis, which was induced by angiotensin II (Ang II) infusion. Results: Ang II infusion was associated with a 4–5-fold increase in fibrosis signal in the tissue of the left ventricle, compared to the control group (0•22±0•10 to 1•08±0•53%; P < 0•001). After treatment with rhubarb pectin, fibrosis was reduced by 57% vs. Ang II alone while this reduction was 30% with the well-known MCP (P = NS, P < 0•05). Treatment was associated with a reduced cardiac inflammatory response and preserved cardiac function. Conclusion: The galectin-3 inhibitor natural rhubarb pectin has a superior inhibitory capacity over established pectins, substantially attenuates cardiac fibrosis, and preserves cardiac function in vivo. Bioactive pectins are natural sources of galectin-3 inhibitors and may be helpful in the prevention of heart failure or other diseases characterized by fibrosis. Funding: Dr. Meijers is supported by the Mandema-Stipendium of the Junior Scientific Masterclass 2020-10, University Medical Center Groningen and by the Netherlands Heart Foundation (Dekkerbeurs 2021)Dr. de Boer is supported by the Netherlands Heart Foundation (CVON SHE-PREDICTS-HF, grant 2017-21; CVON RED-CVD, grant 2017-11; CVON PREDICT2, grant 2018-30; and CVON DOUBLE DOSE, grant 2020B005), by a grant from the leDucq Foundation (Cure PhosphoLambaN induced Cardiomyopathy (Cure-PLaN), and by a grant from the European Research Council (ERC CoG 818715, SECRETE-HF)

The High-Risk Plaque Initiative: Primary Prevention of Atherothrombotic Events in the Asymptomatic Population

The High-Risk Plaque (HRP) Initiative is a research and development effort to advance the understanding, recognition, and management of asymptomatic individuals at risk for a near-term atherothrombotic event such as myocardial infarction or stroke. Clinical studies using the newest technologies have been initiated, including the BioImage Study in which novel approaches are tested in a typical health plan population. Asymptomatic at-risk individuals were enrolled, including a survey-only group (n = 865), a group undergoing traditional risk factor scoring (n = 718), and a group in which all were assessed for both risk factors and subclinical atherosclerosis (n = 6104). The latter two groups underwent baseline examination in a dedicated mobile facility equipped with advanced imaging tools suitable for noninvasive screening for subclinical atherosclerosis (coronary artery calcium by computed tomography [CT], carotid and aortic disease by ultrasound, and ankle-brachial index). Selected participants were offered advanced imaging (contrast-enhanced CT, magnetic resonance imaging, and positron emission tomography/CT). Plasma, PAXgene RNA, and DNA samples were obtained for biomarker discovery studies. All individuals will be followed until 600 major atherothrombotic events have occurred in those undergoing imaging

Technology-Based Disease Management: A Low-Cost, High-Value Solution for the Management of Chronic Disease

Background: Although information technology applications are part of all disease management programs, most programs involve extensive nurse interventions. Objective: To present clinical and financial outcomes data from One Health Plan's technology-based program(s), which provide asthma, diabetes mellitus, and cardiovascular care to over 90 000 participants. Methods: The programs are designed to support the health plan's patient population with asthma, diabetes, congestive heart failure, and coronary artery disease. Data from the health plan's medical and pharmaceutical claims were used to identify the total patient population. The program(s) use extensively mail, Internet, and Interactive Voice Response (IVR) services with only limited nurse interventions to engage the patients and intervene in their care. Patient engagement consisted of an introductory mailing supported by follow-up mailing. The objective was for the targeted patient to respond by completing a survey on paper, over the Internet, or via IVR. The CareResults SM program, uses participant-reported information to risk stratify the population and to track patients progress as part of the measurements of the program's results. The risk stratification algorithm scores the participant's clinical status and ability to self-manage their care. Both dimensions impact the participant's risk score, which in turn determines the follow-up activities. CareResults SM mails a personalized feedback booklet as part of a care kit to educate the participant on the current treatment protocols. The goal is to help the participant recognize good healthcare and teach them to work with their physicians to achieve this. Results: The programs demonstrate that improved outcomes can be rapidly achieved for a large number of participants without costly nurse interventions. One Health Plan offered the program to over 250 000 members in the year 2000 and had over 93 000 elect to participate. Improved clinical outcomes were demonstrated for asthma, diabetes, and the cardiovascular diseases. Highlights include a 55.2% increase in candidates with diabetes receiving glycosylated hemoglobin A1c test, and a 27% self-reported increase in the use of low-dose aspirin for participants with a cardiovascular condition. Financially, current analysis comparing 1999 costs to 2000 costs indicates that the program's per member per year net savings ranged from $US300 to$US1000 depending on the specific disease state. In all cases, the programs demonstrated a significant positive gross saving. Conclusion: One Health Plan's experience demonstrates that the technology-based CareResults SM program produces positive financial and clinical results without significant nurse interventions.Asthma, Cardiovascular disorders, Diabetes mellitus, Disease management programmes, Pharmacoeconomics

The BioImage Study: novel approaches to risk assessment in the primary prevention of atherosclerotic cardiovascular disease--study design and objectives

The identification of asymptomatic individuals at risk for near-term atherothrombotic events to ensure optimal preventive treatment remains a challenging goal. In the BioImage Study, novel approaches are tested in a typical health-plan population. Based on certain demographic and risk characteristics on file with Humana Inc, a total of 7,687 men 55 to 80 years of age and women 60 to 80 years of age without evidence of atherothrombotic disease but presumed to be at risk for near-term atherothrombotic events were enrolled between January 2008 and June 2009. Those who met the prespecified eligibility criteria were randomized to a telephonic health survey only (survey only: n = 865), standard risk assessment (Framingham only: n = 718), or comprehensive risk assessment in a dedicated mobile facility equipped with advanced imaging tools (n = 6,104). Baseline examination included assessment of cardiovascular risk factors and screening for subclinical (asymptomatic) atherosclerosis with quantification of coronary artery calcification by computed tomography (CT), measurement of intima-media thickness, presence of carotid atherosclerotic plaques and abdominal aortic aneurysm by ultrasound, and ankle brachial index. Participants with one or more abnormal screening test results underwent advanced imaging with contrast-enhanced magnetic resonance imaging for carotid and aortic plaques, contrast-enhanced coronary CT angiography for luminal stenosis and noncalcified plaques, and 18F-fluorodeoxyglucose-positron emission tomography/CT for carotid and aortic plaque inflammation. Plasma, PAXgene RNA, and DNA samples were obtained, frozen, and stored for future biomarker discovery studies. All individuals will be followed until 600 major atherothrombotic events have occurred in those undergoing imaging. The BioImage Study will help identify those patients with subclinical atherosclerosis who are at risk for near-term atherothrombotic events and enable a more personalized management of car

Beneficial Effects of Mineralocorticoid Receptor Pathway Blockade against Endothelial Inflammation Induced by SARS-CoV-2 Spike Protein

Background: Vascular endothelial cells activation and dysfunction mediate inflammation and abnormal coagulation in COVID-19 patients. Mineralocorticoid receptor (MR) signaling and its downstream target Galectin-3 (Gal-3) are known to mediate cardiovascular inflammation and might be involved in the pathogenesis of COVID-19 complications. Accordingly, we aimed to investigate the potential beneficial effects of MR antagonism and Gal-3 inhibition on the inflammatory response induced by SARS-CoV-2 Spike protein in human aortic endothelial cells (HAECs). Methods: HAECs were treated with recombinant SARS-COV2 Spike (S) protein. MR antagonists (namely spironolactone and eplerenone) or the Gal-3 inhibitor G3P-01 were supplemented before and after S protein challenge. HAECs supernatants were assessed by ELISA or Western blotting. Results: HAECs treated with recombinant S protein resulted in enhanced secretion of inflammatory molecules (interleukin-6, monocyte chemoattractant protein-1, interleukin-18, interleukin-27, and interferon-γ) as well as in the thrombosis marker plasminogen activator inhibitor (PAI)-1. This was prevented and reversed by both MR antagonists and G3P-01. Conclusions: These findings indicate that MR/Gal-3 pathway blockade could be a promising option to reduce endothelial inflammation in SARS-CoV-2 infection