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Perturbations in myocardial perfusion and oxygen balance in swine with multiple risk factors: a novel model of ischemia and no obstructive coronary artery disease
In conclusion, common comorbidities in swine result in CMD, in the absence of appreciable atherosclerosis, which is severe en ough to produce perturbations in myocardial oxygen balance, particularly during exercise, resembling key features of INOCA.
Source: Basic Research in Cardiology - February 24, 2020 Category: Cardiology Source Type: research

Use of a bioengineered antioxidant in mouse models of metabolic syndrome.
Conclusions: PEG-HCC can improve some parameters of disease in these models and this may be due to a resulting increase in peripheral insulin sensitivity. However, additional studies are needed to elucidate how PEG-HCCs are producing these effects. PMID: 31937152 [PubMed - as supplied by publisher]
Source: Expert Opinion on Investigational Drugs - January 17, 2020 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

Cardiac hypertrophy with obesity is augmented after pregnancy in C57BL/6 mice
ConclusionsThese results suggest that the combined effects of pregnancy and obesity augment cardiac hypertrophy and promote remodeling. The rising prevalence of CVD in premenopausal women may be attributed to an increased prevalence of women entering pregnancy with an overweight or obese BMI.
Source: Biology of Sex Differences - December 15, 2019 Category: Biology Source Type: research

Why You Should Start Thinking About Your Cholesterol Earlier
High cholesterol is known to be one of the primary risk factors for heart disease, since it can contribute to plaque buildup in the arteries. But even though the U.S. Centers for Disease Control and Prevention recommends regular cholesterol testing starting around age 20, many Americans don’t give cholesterol—or heart disease, for that matter—much thought until later in life. A new modeling study published in the Lancet gives extra reason not to put off cholesterol screening and treatment. It confirms that high blood levels of “bad” (or non-HDL) cholesterol are associated with a greater risk o...
Source: TIME: Health - December 4, 2019 Category: Consumer Health News Authors: Jamie Ducharme Tags: Uncategorized Research Source Type: news

Delayed Administration of Angiotensin II Type 2 Receptor (AT2R) Agonist Compound 21 Prevents the Development of Post-stroke Cognitive Impairment in Diabetes Through the Modulation of Microglia Polarization
AbstractA disabling consequence of stroke is cognitive impairment, occurring in 12% –48% of patients, for which there is no therapy. A critical barrier is the lack of understanding of how post-stroke cognitive impairment (PSCI) develops. While 70% of stroke victims present with comorbid diseases such as diabetes and hypertension, the limited use of comorbid disease models in prec linical research further contributes to this lack of progress. To this end, we used a translational model of diabetes to study the development of PSCI. In addition, we evaluated the application of compound 21 (C21), an angiotensin II Type 2 rece...
Source: Translational Stroke Research - December 2, 2019 Category: Neurology Source Type: research

Smooth muscle cell-specific knockout of FBW7 exacerbates intracranial atherosclerotic stenosis.
Abstract Intracranial atherosclerotic stenosis (ICAS), the most common cause of stroke worldwide, is associated with high risk of recurrent ischemic stroke. F-box and WD repeat domain containing protein 7 (FBW7), an ubiquitin E3 ligase, is recently suggested to be involved in atherogenesis. However, whether FBW7 affects cerebrovascular remodeling during ICAS remains unknowns. We found that the expression of FBW7 was decreased in mouse brain microvessels from high-fat diet (HFD)-fed atherosclerotic mice. The reduced FBW7 expression was negatively associated with the remodeling of middle cerebral artery (MCA). Speci...
Source: Neurobiology of Disease - August 20, 2019 Category: Neurology Authors: Shen Y, Chen X, Chi C, Wang H, Xue J, Su D, Wang H, Li M, Liu B, Dong Q Tags: Neurobiol Dis Source Type: research

Obesity-induced type 2 diabetes impairs neurological recovery after stroke in correlation with decreased neurogenesis and persistent atrophy of parvalbumin-positive interneurons
Type 2 diabetes (T2D) hampers stroke recovery though largely undetermined mechanisms. Few preclinical studies have investigated the effect of genetic/toxin-induced diabetes on long-term stroke recovery. However, the effects of obesity-induced T2D are mostly unknown. We aimed to investigate whether obesity-induced T2D worsens long-term stroke recovery through the impairment of brain's self-repair mechanisms - stroke-induced neurogenesis and parvalbumin (PV)+ interneurons-mediated neuroplasticity. To mimic obesity-induced T2D in the middle-age, C57bl/6j mice were fed 12 months with high-fat diet and subjected to transient mi...
Source: Clinical Science - June 23, 2019 Category: Biomedical Science Authors: Pintana, H., Lietzau, G., Augestad, I. L., Chiazza, F., Nystrom, T., Patrone, C., Darsalia, V. Tags: PublishAheadOfPrint Source Type: research

Mild hypothermia alleviates diabetes aggravated cerebral ischemic injury via activating autophagy and inhibiting pyroptosis.
In conclusion, mild hypothermia alleviated diabetes aggravated cerebral ischemic injury via activating autophagy and inhibiting pyroptosis. PMID: 31082455 [PubMed - as supplied by publisher]
Source: Brain Research Bulletin - May 9, 2019 Category: Neurology Authors: Tu Y, Guo C, Song F, Huo Y, Geng Y, Guo M, Bao H, Wu X, Fan W Tags: Brain Res Bull Source Type: research

Challenge to the Intestinal Mucosa During Sepsis
Conclusion The impact of sepsis on the gut is manifold, e.g., sepsis mediated alteration of the gut-blood barrier and increase in the intestinal permeability, which may correlate with the phenomena of bacterial translocation and lymphatic activation (“toxic-lymph”). Systemic consequences of sepsis are widespread and concern to the coagulative system, the microbiome as well as enzymes, such as pancreatic proteases, MMPs and IAPs. Nevertheless, the therapeutic approaches for modulating the mucosal immune system are still rarely effective in daily routine. Recent published studies showing that treatment with ...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

FDG atrial uptake is associated with an increased prevalence of stroke in patients with atrial fibrillation
ConclusionsThis study shows a significant correlation between FDG atrial uptake and AF. While inconsistent, this pattern seems to be associated with an increased prevalence of cardioembolic stroke.
Source: European Journal of Nuclear Medicine and Molecular Imaging - April 27, 2019 Category: Nuclear Medicine Source Type: research

Atrial Transcriptional Profiles of Molecular Targets Mediating Electrophysiological Function in Aging and Pgc-1 β Deficient Murine Hearts
Conclusion: These findings limit the possible roles of gene transcriptional changes in previously reported age-dependent pro-arrhythmic electrophysiologial changes observed in Pgc-1β-/- atria to an altered Ca2+-ATPase (Atp2a2) expression. This directly parallels previously reported arrhythmic mechanism associated with p21-activated kinase type 1 deficiency. This could add to contributions from the direct physiological outcomes of mitochondrial dysfunction, whether through reactive oxygen species (ROS) production or altered Ca2+ homeostasis. Introduction Atrial arrhythmias constitute a major public health pro...
Source: Frontiers in Physiology - April 23, 2019 Category: Physiology Source Type: research

Is Aberrant Reno-Renal Reflex Control of Blood Pressure a Contributor to Chronic Intermittent Hypoxia-Induced Hypertension?
This study demonstrated unaltered vascular conductance in response to lumbar sympathetic stimulation in CIH-exposed rats. Aortic compliance was increased and estimated blood volume was unchanged in CIH-exposed rats. Increased blood pressure was related to an increase in cardiac output, which was confirmed by echocardiography (Lucking et al., 2014). It is suggested therefore that hypertension in the CIH model can be evoked by over-excitation of the cardiac arm of sympathetic nervous system (SNS), even before mechanisms of enhanced peripheral vasoconstriction and endothelial dysfunction are initiated (Naghshin et al., 2009)....
Source: Frontiers in Physiology - April 23, 2019 Category: Physiology Source Type: research

Increasing Upstream Chromatin Long –Range Interactions May Favor Induction of Circular RNAs in LysoPC-Activated Human Aortic Endothelial Cells
We examined the sponging potential of all significantly changed circRNAs using the CircInteractome database (Montefiori et al., 2018), recording two miRNAs with four or more predicted binding sites in a single circRNA transcript, a threshold above which meaningful sponging activity is likely to occur Memczak et al. (2013). Another four significantly changed circRNAs are experimentally shown to sponge miRNAs (Dudekula et al., 2016; Chen et al., 2017; Yan et al., 2017; Wang et al., 2018), for six total circRNAs with miRNA sponging activity including miR125, miR143, miR1272, miR153, miR515-5p, and miR196a-5p (Table 4). In Fig...
Source: Frontiers in Physiology - April 17, 2019 Category: Physiology Source Type: research

Nrf2 as a Potential Mediator of Cardiovascular Risk in Metabolic Diseases
Conclusion Activation of the Nrf2-dependent antioxidant system plays an important role in cell defense against oxidative stress damage, whereas the insufficiency of the Nrf2 system is associated with multiple aspects of the genesis and progression of metabolic diseases, posing a great risk to the cardiovascular system (Figure 1). The systemic increase of Nrf2 activity by several activators may be beneficial in the treatment of metabolic diseases. In addition, selective upregulation of Nrf2 genes may represent a potential therapy in obesity, diabetes and atherosclerosis. Looking to the future, experimental research that el...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

The Discovery and Development of Liraglutide and Semaglutide
We describe one such approach, albumin binding, and explain how it was applied in the development of the human GLP-1 analog liraglutide once daily and, subsequently, semaglutide once weekly. The pharmacology of these two long-acting GLP-1 analogs, in terms of improving glycemic control, reducing body weight and decreasing cardiovascular (CV) risk, is also reviewed, together with some novel biology. In addition, we describe the importance of accurate target (GLP-1 receptor) tissue expression analysis. Now an established class of agents, GLP-1-based therapies represent a significant advance in the treatment of T2D. All curr...
Source: Frontiers in Endocrinology - April 11, 2019 Category: Endocrinology Source Type: research

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