Infodemics and infodemiology: a short history, a long future

An “infodemic” is defined as “an overabundance of information – some accurate and some not – occurring during an epidemic”. This paper describes the characteristics of an infodemic, which combines an inordinately high volume of information (leading to problems relating to locating the information, storage capacity, ensuring quality, visibility and validity) and rapid output (making it hard to assess its value, manage the gatekeeping process, apply results, track its history, and leading to a waste of effort). This is bound up with the collateral growth of misinformation, disinformation and malinformation. Solutions to the problems posed by an infodemic will be sought in improved technology and changed social and regulatory frameworks. One solution could be a new trusted top-level domain for health information. The World Health Organization has so far made two unsuccessful attempts to create such a domain, but it is suggested this could be attempted again, in the light of the COVID-19 infodemic experience. The vital role of reliable information in public health should also be explicitly recognized in the Sustainable Development Goals, with explicit targets. All countries should develop knowledge preparedness plans for future emergencies.

Glycation of Apolipoprotein A-IV Impairs Angiogenesis Through The Orphan Nuclear Receptor Nur77

Background Apo A-Ⅳ played an key role in Cardiovascular diseases, but the effect and mechanism of glycated apo A-Ⅳ on angiogenesis remains unclear. Methods In this study, we demonstrated that oral administration of glycated apoA-Ⅳ impaired blood perfusion recovery in a mouse hind-limb ischemia model. A reduction in blood perfusion recovery at day 21 was observed in the ischemic tissue of apoA-Ⅳ and glycated apoA-Ⅳ-treated mice. Results In this study, we demonstrated that glycated apo A-Ⅳ impaired blood perfusion recovery in a mouse hind-limb ischemia model. And in vitro study also showed that glycated apo A-Ⅳ inhibited the migration, proliferation, and tube-formation abilities of endothelial cells. Further research revealed that glycated apo A-Ⅳ regulated angiogenesis partly by interrupting Nur77. In addition, CML levels were increased in patients with Lower limb circulation (n = 30) compared with those with no limb circulation(n = 50). Conclusions We found impaired angiogenesis induced by glycated apo A-Ⅳ might contribute to poor coronary collateral growth by inhibit the expression of Nur77.

Coronary Microvascular Adaptations Distal to Epicardial Artery Stenosis

Until recently, epicardial coronary stenosis has been considered the primary outcome of coronary heart disease and clinical interventions have been dedicated primarily to identification and removal of flow-limiting stenoses. However, a growing body of literature indicates that both epicardial stenosis and microvascular dysfunction contribute to damaging myocardial ischemia. In this review, we discuss the co-existence of macro- and microvascular disease, and how the structure and function of the distal microcirculation is impacted by the hemodynamic consequences of an epicardial, flow-limiting stenosis. Mechanisms of endothelial dysfunction as well as alterations of smooth muscle function in the coronary microcirculation distal to stenosis are discussed. Risk factors including diabetes, metabolic syndrome, and aging exacerbate microvascular dysfunction in the myocardium distal to a stenosis, and our current understanding of the role of these factors in limiting collateralization and angiogenesis of the ischemic myocardium is presented. Importantly, exercise training has been shown to promote collateral growth and improve microvascular function distal to stenosis; thus, the current literature reporting the mechanisms that underlie the beneficial effects of exercise training in the microcirculation distal to epicardial stenosis is reviewed. We also discuss recent studies of therapeutic interventions designed to improve microvascular function and stimulate angiogenesis in clinically relevant animal models of epicardial stenosis and microvascular disease. Finally, microvascular adaptation to removal of epicardial stenosis is considered.

Heat therapy improves body composition and muscle function, but does not affect capillary or collateral growth in a model of obesity and hindlimb ischemia

Heat therapy (HT) has emerged as a potential adjunctive therapy to alleviate the symptoms of peripheral artery disease (PAD), but the mechanisms underlying the positive effects of this treatment modality remain undefined. Using a model of diet-induced obesity (DIO) and ischemia-induced muscle damage, we tested the hypothesis that HT would alter body composition, promote vascular growth and mitochondrial biogenesis, and improve skeletal muscle function. Male DIO C57Bl/6J mice underwent bilateral ligation of the femoral artery and were randomly allocated to receive HT or a control intervention for 30 min daily over 3 weeks. When compared to a group of lean, sham-operated animals, ligated DIO mice exhibited increases in body and fat masses, exercise intolerance and contractile dysfunction of the isolated soleus (SOL) and extensor digitorum longus (EDL) muscles. Repeated HT averted an increase in body mass induced by high-fat feeding due to reduced fat accrual. Fat mass was ~25% and 29% lower in the HT group relative to controls after 2 and 3 weeks of treatment, respectively. Muscle mass relative to body mass and maximal absolute force of the EDL, but not SOL, were higher in animals exposed to HT. There were no group differences in skeletal muscle capillarization, the expression of angiogenic factors, mitochondrial content and the diameter of the gracilis arteries. These findings indicate that HT reduces diet-induced fat accumulation and rescues skeletal muscle contractile dysfunction. This practical treatment may prove useful for diabetic and obese PAD patients who are unable to undergo conventional exercise regimens.

The Impact of Estrogen Receptor in Arterial and Lymphatic Vascular Diseases

The lower incidence of cardiovascular diseases in pre-menopausal women compared to men is well-known documented. This protection has been largely attributed to the protective effect of estrogens, which exert many beneficial effects against arterial diseases, including vasodilatation, acceleration of healing in response to arterial injury, arterial collateral growth and atheroprotection. More recently, with the visualization of the lymphatic vessels, the impact of estrogens on lymphedema and lymphatic diseases started to be elucidated. These estrogenic effects are mediated not only by the classic nuclear/genomic actions via the specific estrogen receptor (ER) α and β, but also by rapid extra-nuclear membrane-initiated steroid signaling (MISS). The ERs are expressed by endothelial, lymphatic and smooth muscle cells in the different vessels. In this review, we will summarize the complex vascular effects of estrogens and selective estrogen receptor modulators (SERMs) that have been described using different transgenic mouse models with selective loss of ERα function and numerous animal models of vascular and lymphatic diseases.

IL10 Alters Peri-Collateral Macrophage Polarization and Hind-Limb Reperfusion in Mice after Femoral Artery Ligation

Arteriogenesis is a process by which a pre-existing arterioarterial anastomosis develops into a functional collateral network following an arterial occlusion. Alternatively activated macrophages polarized by IL10 have been described to promote collateral growth. This study investigates the effect of different levels of IL10 on hind-limb reperfusion and the distribution of perivascular macrophage activation types in mice after femoral artery ligation (FAL). IL10 and anti-IL10 were administered before FAL and the arteriogenic response was measured by Laser-Doppler-Imaging perioperatively, after 3, 7, and 14 d. Reperfusion recovery was accelerated when treated with IL10 and impaired with anti-IL10. Furthermore, symptoms of ischemia on ligated hind-limbs had the highest incidence after application of anti-IL10. Perivascular macrophages were immunohistologically phenotyped using CD163 and CD68 in adductor muscle segments. The proportion of alternatively activated macrophages (CD163+/CD68+) in relation to classically activated macrophages (CD163−/CD68+) observed was the highest when treated with IL10 and suppressed with anti-IL10. This study underlines the proarteriogenic response with increased levels of IL10 and demonstrates an in-vivo alteration of macrophage activation types in the perivascular bed of growing collaterals.

The Lipopeptide MALP-2 Promotes Collateral Growth

Beyond their role in pathogen recognition and the initiation of immune defense, Toll-like receptors (TLRs) are known to be involved in various vascular processes in health and disease. We investigated the potential of the lipopeptide and TLR2/6 ligand macrophage activating protein of 2-kDA (MALP-2) to promote blood flow recovery in mice. Hypercholesterolemic apolipoprotein E (Apoe)-deficient mice were subjected to microsurgical ligation of the femoral artery. MALP-2 significantly improved blood flow recovery at early time points (three and seven days), as assessed by repeated laser speckle imaging, and increased the growth of pre-existing collateral arteries in the upper hind limb, along with intimal endothelial cell proliferation in the collateral wall and pericollateral macrophage accumulation. In addition, MALP-2 increased capillary density in the lower hind limb. MALP-2 enhanced endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) release from endothelial cells and improved the experimental vasorelaxation of mesenteric arteries ex vivo. In vitro, MALP-2 led to the up-regulated expression of major endothelial adhesion molecules as well as their leukocyte integrin receptors and consequently enhanced the endothelial adhesion of leukocytes. Using the experimental approach of femoral artery ligation (FAL), we achieved promising results with MALP-2 to promote peripheral blood flow recovery by collateral artery growth.