Displaying publications 1 - 20 of 27 in total

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  1. Rostam MA, Piva TJ, Rezaei HB, Kamato D, Little PJ, Zheng W, et al.
    Clin Exp Pharmacol Physiol, 2015 Feb;42(2):117-24.
    PMID: 25377120 DOI: 10.1111/1440-1681.12335
    Peptidyl-prolyl cis/trans isomerases (PPIases) are a conserved group of enzymes that catalyse the conversion between cis and trans conformations of proline imidic peptide bonds. These enzymes play critical roles in regulatory mechanisms of cellular function and pathophysiology of disease. There are three different classes of PPIases and increasing interest in the development of specific PPIase inhibitors. Cyclosporine A, FK506, rapamycin and juglone are known PPIase inhibitors. Herein, we review recent advances in elucidating the role and regulation of the PPIase family in vascular disease. We focus on peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1), an important member of the PPIase family that plays a role in cell cycle progression, gene expression, cell signalling and cell proliferation. In addition, Pin1 may be involved in atherosclerosis. The unique role of Pin1 as a molecular switch that impacts on multiple downstream pathways necessitates the evaluation of a highly specific Pin1 inhibitor to aid in potential therapeutic drug discovery.
    Matched MeSH terms: Cardiovascular Diseases/metabolism*
  2. Sousa Fialho MDL, Abd Jamil AH, Stannard GA, Heather LC
    Biochim Biophys Acta Mol Basis Dis, 2019 04 01;1865(4):831-843.
    PMID: 30266651 DOI: 10.1016/j.bbadis.2018.09.024
    Cardiovascular disease (CVD) accounts for the largest number of deaths worldwide, necessitating the development of novel treatments and prevention strategies. Given the huge energy demands placed on the heart, it is not surprising that changes in energy metabolism play a key role in the development of cardiac dysfunction in CVD. A reduction in oxygen delivery to the heart, hypoxia, is sensed and responded to by the hypoxia-inducible factor (HIF) and its family of proteins, by regulating the oxygen-dependent signalling cascade and subsequent response. Hypoxia is one of the main drivers of metabolic change in ischaemic disease and myocardial infarction, and we therefore suggest that HIF may be an attractive therapeutic target. In this review, we assess cardiac energy metabolism in health and disease, and how these can be regulated by HIF-1α activation. We then present an overview of research in the field of hypoxia-mimetic drugs recently developed in other treatment fields, which provide insight into the potential of systemic HIF-1α activation therapy for treating the heart.
    Matched MeSH terms: Cardiovascular Diseases/metabolism*
  3. Balakumar P, Anand-Srivastava MB, Jagadeesh G
    Pharmacol Res, 2017 11;125(Pt A):1-3.
    PMID: 28711403 DOI: 10.1016/j.phrs.2017.07.003
    Matched MeSH terms: Cardiovascular Diseases/metabolism
  4. Aminuddin A, Chellappan K, Maskon O, Zakaria Z, Karim AA, Ngah WZ, et al.
    Saudi Med J, 2014 Feb;35(2):138-46.
    PMID: 24562512
    To determine the association between carotid femoral pulse wave velocity (PWVCF) and augmentation index (AI) with future cardiovascular disease (CVD) risk, and to assess whether high sensitivity C-reactive protein (hs-CRP) is an important mediator towards these vascular changes, among young men.
    Matched MeSH terms: Cardiovascular Diseases/metabolism*
  5. Lee ECS, Elhassan SAM, Lim GPL, Kok WH, Tan SW, Leong EN, et al.
    Biomed Pharmacother, 2019 Mar;111:198-208.
    PMID: 30583227 DOI: 10.1016/j.biopha.2018.12.052
    For many years, circular ribonucleic acids (circRNAs) have been counted as aberrant splicing by-products. Advanced bioinformatics analysis and deep sequencing techniques have allowed researchers to discover more interesting facts about circRNAs. Intriguing evidence has shed light on the functions of circRNAs in many tissues. Furthermore, emerging reports showed that circRNAs are found abundantly in saliva and blood samples, suggesting that circRNAs are potential clinical biomarkers for human embryonic development, diseases progression and prognosis, in addition to its role in organogenesis and pathogenesis. The implementation of circRNAs in human developmental stages and diseases would be a tremendous discovery in the science and medical field. Therefore, circRNAs have been studied for its biological function as well as its implication in various human diseases. The aim of this review is to highlight the importance of circRNAs in cardiac, respiratory, nervous, endocrine and digestive systems. In addition, the role and impact of circRNAs in, cardiogenesis, neurogenesis and cancer have been discussed.
    Matched MeSH terms: Cardiovascular Diseases/metabolism
  6. Khazdouz M, Djalalinia S, Sarrafi Zadeh S, Hasani M, Shidfar F, Ataie-Jafari A, et al.
    Biol Trace Elem Res, 2020 Jun;195(2):373-398.
    PMID: 31494808 DOI: 10.1007/s12011-019-01870-9
    The prevalence of cardiometabolic risk factors has been increasing worldwide. The results of reported studies on the effects of zinc supplementation on cardiometabolic risk factors are unequivocal. This systematic review and meta-analysis of randomized controlled trials was conducted to evaluate the effects of zinc supplementation on cardiometabolic risk factors. A systematic search was conducted through international databases (PubMed/Medline, Institute of Scientific Information, and Scopus) until December 2018 to include all randomized controlled trials (RCT), quasi-RCT, and controlled clinical trials which assessed the effect of zinc supplementation on cardiometabolic risk factors including lipid profile, glycemic indices, blood pressure, and anthropometric indices. Random- or fixed-effects meta-analysis method was used to estimate the standardized mean difference (SMD) and 95% confidence interval (CI). A total of 20 studies were included in the meta-analysis, which included a total of 1141 participants in the intervention group. Meta-analysis showed that zinc supplementation significantly decreased plasma levels of triglyceride (SMD - 0.66, 95% CI - 1.27, - 0.06), very-low-density lipoprotein (SMD - 1.59, 95% CI - 2.86, - 0.31), and total cholesterol (SMD - 0.65, 95% CI - 1.15, - 0.15). Similarly, zinc supplementation significantly decreased fasting blood glucose (SMD - 0.52, 95% CI - 0.96, - 0.07) and HbA1c (SMD - 0.64, 95% CI - 1.27, - 0.02). The effects of zinc supplementation on blood pressure and anthropometric indices were not statistically significant (P > 0.05). Zinc supplements had beneficial effects on glycemic indices and lipid profile. Thus, it appeared that zinc supplementation might be associated with a decrease in cardiometabolic risk factors contributing to a reduction in risk of atherosclerosis.
    Matched MeSH terms: Cardiovascular Diseases/metabolism
  7. Syafruddin SE, Mohtar MA, Wan Mohamad Nazarie WF, Low TY
    Biomolecules, 2020 09 28;10(10).
    PMID: 32998281 DOI: 10.3390/biom10101378
    The Krüppel-like factors (KLFs) family of proteins control several key biological processes that include proliferation, differentiation, metabolism, apoptosis and inflammation. Dysregulation of KLF functions have been shown to disrupt cellular homeostasis and contribute to disease development. KLF6 is a relevant example; a range of functional and expression assays suggested that the dysregulation of KLF6 contributes to the onset of cancer, inflammation-associated diseases as well as cardiovascular diseases. KLF6 expression is either suppressed or elevated depending on the disease, and this is largely due to alternative splicing events producing KLF6 isoforms with specialised functions. Hence, the aim of this review is to discuss the known aspects of KLF6 biology that covers the gene and protein architecture, gene regulation, post-translational modifications and functions of KLF6 in health and diseases. We put special emphasis on the equivocal roles of its full-length and spliced variants. We also deliberate on the therapeutic strategies of KLF6 and its associated signalling pathways. Finally, we provide compelling basic and clinical questions to enhance the knowledge and research on elucidating the roles of KLF6 in physiological and pathophysiological processes.
    Matched MeSH terms: Cardiovascular Diseases/metabolism
  8. Vellasamy S, Murugan D, Abas R, Alias A, Seng WY, Woon CK
    Molecules, 2021 Aug 17;26(16).
    PMID: 34443563 DOI: 10.3390/molecules26164976
    Paeonol is a naturally existing bioactive compound found in the root bark of Paeonia suffruticosa and it is traditionally used in Chinese medicine for the prevention and management of cardiovascular diseases. To date, a great deal of studies has been reported on the pharmacological effects of paeonol and its mechanisms of action in various diseases and conditions. In this review, the underlying mechanism of action of paeonol in cardiovascular disease has been elucidated. Recent studies have revealed that paeonol treatment improved endothelium injury, demoted inflammation, ameliorated oxidative stress, suppressed vascular smooth muscle cell proliferation, and repressed platelet activation. Paeonol has been reported to effectively protect the cardiovascular system either employed alone or in combination with other traditional medicines, thus, signifying it could be a hypothetically alternative or complementary atherosclerosis treatment. This review summarizes the biological and pharmacological activities of paeonol in the treatment of cardiovascular diseases and its associated underlying mechanisms for a better insight for future clinical practices.
    Matched MeSH terms: Cardiovascular Diseases/metabolism
  9. Nishimura A, Sunggip C, Oda S, Numaga-Tomita T, Tsuda M, Nishida M
    Pharmacol Ther, 2017 Dec;180:113-128.
    PMID: 28648830 DOI: 10.1016/j.pharmthera.2017.06.010
    Purinergic signaling, mediated mainly by G protein-coupled P2Y receptors (P2YRs), is now attracting attention as a new therapeutic target for preventing or treating cardiovascular diseases. Observations using mice with genetically modified P2YRs and/or treated with a pharmacological P2YR inhibitor have helped us understand the physiological and pathological significance of P2YRs in the cardiovascular system. P2YR-mediated biological functions are predominantly activated by mononucleotides released from non-adrenergic, non-cholinergic nerve endings or non-secretory tissues in response to physical stress or cell injury, though recent studies have suggested the occurrence of ligand-independent P2YR function through receptor-receptor interactions (oligomerization) in several biological processes. In this review, we introduce the functions of P2YRs and possible dimerization with G protein-coupled receptors (GPCRs) in the cardiovascular system. We focus especially on the crosstalk between uridine nucleotide-responsive P2Y6R and angiotensin (Ang) II type1 receptor (AT1R) signaling, and introduce our recent finding that the P2Y6R antagonist MRS2578 interrupts heterodimerization between P2Y6R and AT1R, thereby reducing the risk of AT1R-stimulated hypertension in mice. These results strongly suggest that targeting P2Y6R oligomerization could be an effective new strategy to reduce the risk of cardiovascular diseases.
    Matched MeSH terms: Cardiovascular Diseases/metabolism
  10. Ooi BK, Goh BH, Yap WH
    Int J Mol Sci, 2017 Nov 05;18(11).
    PMID: 29113088 DOI: 10.3390/ijms18112336
    Oxidative stress is an important risk factor contributing to the pathogenesis of cardiovascular diseases. Oxidative stress that results from excessive reactive oxygen species (ROS) production accounts for impaired endothelial function, a process which promotes atherosclerotic lesion or fatty streaks formation (foam cells). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor involved in cellular redox homeostasis. Upon exposure to oxidative stress, Nrf2 is dissociated from its inhibitor Keap-1 and translocated into the nucleus, where it results in the transcriptional activation of cell defense genes. Nrf2 has been demonstrated to be involved in the protection against foam cells formation by regulating the expression of antioxidant proteins (HO-1, Prxs, and GPx1), ATP-binding cassette (ABC) efflux transporters (ABCA1 and ABCG1) and scavenger receptors (scavenger receptor class B (CD36), scavenger receptor class A (SR-A) and lectin-type oxidized LDL receptor (LOX-1)). However, Nrf2 has also been reported to exhibit pro-atherogenic effects. A better understanding on the mechanism of Nrf2 in oxidative stress-induced cardiac injury, as well as the regulation of cholesterol uptake and efflux, are required before it can serve as a novel therapeutic target for cardiovascular diseases prevention and treatment.
    Matched MeSH terms: Cardiovascular Diseases/metabolism*
  11. Ong SB, Kalkhoran SB, Cabrera-Fuentes HA, Hausenloy DJ
    Eur J Pharmacol, 2015 Sep 15;763(Pt A):104-14.
    PMID: 25987420 DOI: 10.1016/j.ejphar.2015.04.056
    The past decade has witnessed a number of exciting developments in the field of mitochondrial dynamics - a phenomenon in which changes in mitochondrial shape and movement impact on cellular physiology and pathology. By undergoing fusion and fission, mitochondria are able to change their morphology between elongated interconnected networks and discrete fragmented structures, respectively. The cardiac mitochondria, in particular, have garnered much interest due to their unique spatial arrangement in the adult cardiomyocyte, and the multiple roles they play in cell death and survival. In this article, we review the role of the mitochondrial fusion and fission proteins as novel therapeutic targets for treating cardiovascular disease.
    Matched MeSH terms: Cardiovascular Diseases/metabolism*
  12. Yusoff K
    Asia Pac J Clin Nutr, 2002;11 Suppl 7:S443-7.
    PMID: 12492632
    Cardiovascular disease, in particular coronary artery disease (CAD), remains the most important cause of morbidity and mortality in developed countries and, in the near future, more so in the developing world. Atherosclerotic plaque formation is the underlying basis for CAD. Growth of the plaque leads to coronary stenosis, causing a progressive decrease in blood flow that results in angina pectoris. Acute myocardial infarction and unstable angina were recently recognised as related to plaque rupture, not progressive coronary stenosis. Acute thrombus formation causes an abrupt coronary occlusion. The characteristics of the fibrin cap, contents of the plaque, rheological factors and active inflammation within the plaque contribute to plaque rupture. Oxidative processes are important in plaque formation. Oxidized low density lipoproteins (LDL) but not unoxidized LDL is engulfed by resident intimal macrophages, transforming them into foam cells which develop into fatty streaks, the precursors of the atherosclerotic plaque. Inflammation is important both in plaque formation and rupture. Animal studies have shown that antioxidants reduce plaque formation and lead to plaque stabilisation. In humans, high intakes of antioxidants are associated with lower incidence of CAD, despite high serum cholesterol levels. This observation suggests a role for inflammation in CAD and that reducing inflammation using antioxidants may ameliorate these processes. Men and women with high intakes of vitamin E were found to have less CAD. Vitamin E supplementation was associated with a significant reduction in myocardial infarction and cardiovascular events in the incidence of recurrent myocardial infarction. In the hierarchy of evidence in evidence-based medicine, data from large placebo-controlled clinical trials is considered necessary. Results from various mega-trials have not shown benefits (nor adverse effects) conferred by vitamin E supplementation, suggesting that vitamin E has no role in the treatment of CAD. These results do not seem to confirm, at the clinical level, the effect of antioxidants against active inflammation during plaque rupture. However, a closer examination of these studies showed a number of limitations, rendering them inconclusive in addressing the role of vitamin E in CAD prevention and treatment. Further studies that specifically address the issue of vitamin E in the pathogenesis of atherosclerosis and in the treatment of CAD need be performed. These studies should use the more potent antioxidant property of alpha-tocotrienol vitamin E.
    Matched MeSH terms: Cardiovascular Diseases/metabolism
  13. Achike FI, Kwan CY
    Clin Exp Pharmacol Physiol, 2003 Sep;30(9):605-15.
    PMID: 12940876
    1. Nitric oxide (NO) is formed enzymatically from l-arginine in the presence of nitric oxide synthase (NOS). Nitric oxide is generated constitutively in endothelial cells via sheer stress and blood-borne substances. Nitric oxide is also generated constitutively in neuronal cells and serves as a neurotransmitter and neuromodulator in non-adrenergic, non-cholinergic nerve endings. Furthermore, NO can also be formed via enzyme induction in many tissues in the presence of cytokines. 2. The ubiquitous presence of NO in the living body suggests that NO plays an important role in the maintenance of health. Being a free radical with vasodilatory properties, NO exerts dual effects on tissues and cells in various biological systems. At low concentrations, NO can dilate the blood vessels and improve the circulation, but at high concentrations it can cause circulatory shock and induce cell death. Thus, diseases can arise in the presence of the extreme ends of the physiological concentrations of NO. 3. The NO signalling pathway has, in recent years, become a target for new drug development. The high level of flavonoids, catechins, tannins and other polyphenolic compounds present in vegetables, fruits, soy, tea and even red wine (from grapes) is believed to contribute to their beneficial health effects. Some of these compounds induce NO formation from the endothelial cells to improve circulation and some suppress the induction of inducible NOS in inflammation and infection. 4. Many botanical medicinal herbs and drugs derived from these herbs have been shown to have effects on the NO signalling pathway. For example, the saponins from ginseng, ginsenosides, have been shown to relax blood vessels (probably contributing to the antifatigue and blood pressure-lowering effects of ginseng) and corpus cavernosum (thus, for the treatment of men suffering from erectile dysfunction; however, the legendary aphrodisiac effect of ginseng may be an overstatement). Many plant extracts or purified drugs derived from Chinese medicinal herbs with proposed actions on NO pathways are also reviewed.
    Matched MeSH terms: Cardiovascular Diseases/metabolism
  14. Ibrahim N', Fairus S, Mohamed IN
    Nutrients, 2020 Jul 10;12(7).
    PMID: 32664390 DOI: 10.3390/nu12072055
    Cardiovascular disease (CVD) is globally known as the number one cause of death with hyperlipidemia as a strong risk factor for CVD. The initiation of drug treatment will be recommended if lifestyle modification fails. However, medicines currently used for improving cholesterol and low-density lipoprotein cholesterols (LDL-C) levels have been associated with various side effects. Thus, alternative treatment with fewer or no side effects needs to be explored. A potential agent, oil palm phenolics (OPP) recovered from the aqueous waste of oil palm milling process contains numerous water-soluble phenolic compounds. It has been postulated that OPP has shown cardioprotective effects via several mechanisms such as cholesterol biosynthesis pathway, antioxidant and anti-inflammatory properties. This review aims to summarize the current evidence explicating the actions of OPP in cardiovascular health and the mechanisms that maybe involved for the cardioprotective effects.
    Matched MeSH terms: Cardiovascular Diseases/metabolism
  15. Ali SS, Ahmad WANW, Budin SB, Zainalabidin S
    Rev Cardiovasc Med, 2020 Jun 30;21(2):225-240.
    PMID: 32706211 DOI: 10.31083/j.rcm.2020.02.49
    In spite of medical advances, cardiovascular disease remains a significant concern, imposing a great burden upon the economy and public health of nations by causing the highest morbidity and mortality cases globally. Moreover, it is well established that inflammation is closely linked to the pathogenesis of cardiovascular diseases. Hence, targeting inflammation seems to be a promising strategy in reducing cardiovascular risks. Currently, the importance of natural products in modern medicine is well recognised and continues to be of interest to the pharmaceutical industry. Phenolic acids are a class of phytochemical compounds that are well-known for their health benefits. They consists of various phytochemical constituents and have been widely studied in various disease models. Research involving both animals and humans has proven that phenolic acids possess cardioprotective properties such as anti-hypertensive, anti-hyperlipidemia, anti-fibrotic and anti-hypertrophy activity. Furthermore, numerous studies have proven that phenolic acids in phytochemical constituents such as gallic acid, caffeic acid and chlorogenic acid are promising anti-inflammatory agents. Hence, in this review, we outline and review recent evidence on the role of phenolic acids and their anti-inflammatory significance in studies published during the last 5 years. We also discuss their possible mechanisms of action in modulating inflammation related to cardiovascular disease.
    Matched MeSH terms: Cardiovascular Diseases/metabolism
  16. Moradipoor S, Ismail P, Etemad A, Wan Sulaiman WA, Ahmadloo S
    Biomed Res Int, 2016;2016:1845638.
    PMID: 27781209 DOI: 10.1155/2016/1845638
    Endothelial dysfunction appears to be an early sign indicating vascular damage and predicts the progression of atherosclerosis and cardiovascular disorders. Extensive clinical and experimental evidence suggests that endothelial dysfunction occurs in Type 2 Diabetes Mellitus (T2DM) and prediabetes patients. This study was carried out with an aim to appraise the expression levels in the peripheral blood of 84 genes related to endothelial cells biology in patients with diagnosed T2DM or prediabetes, trying to identify new genes whose expression might be changed under these pathological conditions. The study covered a total of 45 participants. The participants were divided into three groups: group 1, patients with T2DM; group 2, patients with prediabetes; group 3, control group. The gene expression analysis was performed using the Endothelial Cell Biology RT(2) Profiler PCR Array. In the case of T2DM, 59 genes were found to be upregulated, and four genes were observed to be downregulated. In prediabetes patients, increased expression was observed for 49 genes, with two downregulated genes observed. Our results indicate that diabetic and prediabetic conditions change the expression levels of genes related to endothelial cells biology and, consequently, may increase the risk for occurrence of endothelial dysfunction.
    Matched MeSH terms: Cardiovascular Diseases/metabolism
  17. Arshad MK, Bin Mohamad Fathil MF, Gopinath SC, Ruslinda AR, Md Nor MN, Lam HY, et al.
    Curr Med Chem, 2016;23(37):4270-4284.
    PMID: 27719655
    Cardiovascular disease (CVD) is a major threat to global health, estimated to be the cause 30 % (17.3 million in 2008) of deaths every year, and the number of deaths caused by CVD is expected to increase further, reaching 23.3 million by 2030. Hence, there is a growing demand for simpler sample extraction, rapid screening results, and intervention of the subsequent analysis in emergency units. In this paper, we reviewed CVD biomarkers in blood- and saliva-based specimens. The history of cardiac biomarkers indicates that in the beginning, cardiac troponin I (cTnI) was a widely accepted 'gold standard' marker due to its high specificity and selectivity. Considering the advantages of salivary-based cardiac biomarkers, we examined correlations between non-invasive (salivary) and invasive (blood) diagnoses, and it was found that C-reactive protein (CRP) provides a better correlation. Despite the low abundance of salivary CRP, several reports displayed the detection limit down to pg/ml using existing technologies. Thus, salivary CRP has the potential to be used for future forefront diagnostics for the early assessment of cardiac risks.
    Matched MeSH terms: Cardiovascular Diseases/metabolism
  18. Jaganathan R, Ravindran R, Dhanasekaran S
    Can J Diabetes, 2018 Aug;42(4):446-456.e1.
    PMID: 29229313 DOI: 10.1016/j.jcjd.2017.10.040
    Adipose tissue is an enormously active endocrine organ, secreting various hormones, such as adiponectin, leptin, resistin and visfatin, together with classical cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). All these adipocytokines play significant roles in the regulation of energy metabolism, glucose and lipid metabolism, reproduction, cardiovascular function and immunity. Adipocytokines are significantly regulated by nutritional status and can directly influence other organ systems, including brain, liver and skeletal muscle. Adiponectin plays a key role as an anti-inflammatory hormone. Upregulated expression of resistin, vaspin, apelin and TNF-α plays a significant role in induction of insulin resistance linked with obesity and type 2 diabetes. Ghrelin, the circulating peptide, has been found to stimulate appetite and regulate energy balance. Thus, it can be considered 1 of the candidate genes for obesity and type 2 diabetes. Omentin is a novel adipokine produced by visceral adipose tissue. Circulating levels of omentin are decreased in insulin-resistant states, for example, in obesity and diabetes. IL-6 plays a vital role in regulating the accumulation of lipids intramyocardially. Based on the biologic relevance of these adipocytokines, they can no longer be considered as energy storage sites alone but must also be considered in metabolic control. Hence, the present review summarizes the regulatory roles of adipocytokines in diabetes linked with obesity.
    Matched MeSH terms: Cardiovascular Diseases/metabolism
  19. Mayurasakorn K, Hasanah N, Homma T, Homma M, Rangel IK, Garza AE, et al.
    Metabolism, 2018 Jun;83:92-101.
    PMID: 29410348 DOI: 10.1016/j.metabol.2018.01.012
    BACKGROUND AND PURPOSE: The plasma membrane protein caveolin-1 (CAV-1) has been shown to be involved in modulating glucose homeostasis and the actions of the renin-angiotensin-aldosterone system (RAAS). Caloric restriction (CR) is widely accepted as an effective therapeutic approach to improve insulin sensitivity and reduce the severity of diabetes. Recent data indicate that polymorphisms of the CAV-1 gene are strongly associated with insulin resistance, hypertension and metabolic abnormalities in non-obese individuals. Therefore, we sought to determine whether CR improves the metabolic and cardiovascular (CV) risk factors in the lean CAV-1 KO mice.

    MATERIALS/METHODS: Twelve- to fourteen-week-old CAV-1 knockout (KO) and genetically matched wild-type (WT) male mice were randomized by genotype to one of two dietary regimens: ad libitum (ad lib) food intake or 40% CR for 4 weeks. Three weeks following the onset of dietary restriction, all groups were assessed for insulin sensitivity. At the end of the study, all groups were assessed for fasting glucose, insulin, HOMA-IR, lipids, corticosterone levels and blood pressure (BP). Aldosterone secretion was determined from acutely isolated Zona Glomerulosa cells.

    RESULTS: We confirmed that the CAV-1 KO mice on the ad lib diet display a phenotype consistent with the cardiometabolic syndrome, as shown by higher systolic BP (SBP), plasma glucose, HOMA-IR and aldosterone levels despite lower body weight compared with WT mice on the ad lib diet. CAV-1 KO mice maintained their body weight on the ad lib diet, but had substantially greater weight loss with CR, as compared to caloric restricted WT mice. CR-mediated changes in weight were associated with dramatic improvements in glucose and insulin tolerance in both genotypes. These responses to CR, however, were more robust in CAV-1KO vs. WT mice and were accompanied by reductions in plasma glucose, insulin and HOMA-IR in CAV-1KO but not WT mice. Surprisingly, in the CAV-1 KO, but not in WT mice, CR was associated with increased SBP and aldosterone levels, suggesting that in CAV-1 KO mice CR induced an increase in some CV risk factors.

    CONCLUSIONS: CR improved the metabolic phenotype in CAV-1 KO mice by increasing insulin sensitivity; nevertheless, this intervention also increased CV risk by inappropriate adaptive responses in the RAAS and BP.

    Matched MeSH terms: Cardiovascular Diseases/metabolism*
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