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1.
Key Enzymes for the Mevalonate Pathway in the Cardiovascular System.
Zhang, C, Jin, DD, Wang, XY, Lou, L, Yang, J
Journal of cardiovascular pharmacology. 2021;(2):142-152
Abstract
Isoprenylation is an important post-transcriptional modification of small GTPases required for their activation and function. Isoprenoids, including farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate, are indispensable for isoprenylation by serving as donors of a prenyl moiety to small G proteins. In the human body, isoprenoids are mainly generated by the mevalonate pathway (also known as the cholesterol-synthesis pathway). The hydroxymethylglutaryl coenzyme A reductase catalyzes the first rate-limiting steps of the mevalonate pathway, and its inhibitor (statins) are widely used as lipid-lowering agents. In addition, the FPP synthase is also of critical importance for the regulation of the isoprenoids production, for which the inhibitor is mainly used in the treatment of osteoporosis. Synthetic FPP can be further used to generate geranylgeranyl pyrophosphate and cholesterol. Recent studies suggest a role for isoprenoids in the genesis and development of cardiovascular disorders, such as pathological cardiac hypertrophy, fibrosis, endothelial dysfunction, and fibrotic responses of smooth-muscle cells. Furthermore, statins and FPP synthase inhibitors have also been applied for the management of heart failure and other cardiovascular diseases rather than their clinical use for hyperlipidemia or bone diseases. In this review, we focus on the function of several critical enzymes, including hydroxymethylglutaryl coenzyme A reductase, FPP synthase, farnesyltransferase, and geranylgeranyltransferase in the mevalonate pathway which are involved in regulating the generation of isoprenoids and isoprenylation of small GTPases, and their pathophysiological role in the cardiovascular system. Moreover, we summarize recent research into applications of statins and the FPP synthase inhibitors to treat cardiovascular diseases, rather than for their traditional indications respectively.
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2.
Which Microbes Like My Diet and What Does It Mean for My Heart?
Sawicka-Śmiarowska, E, Moniuszko-Malinowska, A, Kamiński, KA
Nutrients. 2021;(11)
Abstract
Cardiovascular diseases are the most common causes of hospitalization, death and disability in Europe. Despite our knowledge of nonmodifiable and modifiable cardiovascular classical risk factors, the morbidity and mortality in this group of diseases remains high, leading to high social and economic costs. Therefore, it is necessary to explore new factors, such as the gut microbiome, that may play a role in many crucial pathological processes related to cardiovascular diseases. Diet is a potentially modifiable cardiovascular risk factor. Fats, proteins, carbohydrates, vitamins and minerals are nutrients that are essential to the proper function of the human body. The style and composition of the human diet has changed over time, evolving from a hunter-gatherer diet to an industrialized and Westernized modern diet that includes processed products. The relationship between the gut microbiome, diet and cardiovascular diseases is complex and still not fully understood. In this review, we discuss, in the context of diet, why particular microbes occur in individuals and how they can influence the host's cardiovascular system in health and disease. We investigate the role of particular microorganisms and changes in the Firmicutes/Bacteroidetes ratio.
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3.
The application of in utero magnetic resonance imaging in the study of the metabolic and cardiovascular consequences of the developmental origins of health and disease.
Giza, SA, Sethi, S, Smith, LM, Empey, MET, Morris, LE, McKenzie, CA
Journal of developmental origins of health and disease. 2021;(2):193-202
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Abstract
Observing fetal development in utero is vital to further the understanding of later-life diseases. Magnetic resonance imaging (MRI) offers a tool for obtaining a wealth of information about fetal growth, development, and programming not previously available using other methods. This review provides an overview of MRI techniques used to investigate the metabolic and cardiovascular consequences of the developmental origins of health and disease (DOHaD) hypothesis. These methods add to the understanding of the developing fetus by examining fetal growth and organ development, adipose tissue and body composition, fetal oximetry, placental microstructure, diffusion, perfusion, flow, and metabolism. MRI assessment of fetal growth, organ development, metabolism, and the amount of fetal adipose tissue could give early indicators of abnormal fetal development. Noninvasive fetal oximetry can accurately measure placental and fetal oxygenation, which improves current knowledge on placental function. Additionally, measuring deficiencies in the placenta's transport of nutrients and oxygen is critical for optimizing treatment. Overall, the detailed structural and functional information provided by MRI is valuable in guiding future investigations of DOHaD.
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4.
Vitamin D Effects on Bone Homeostasis and Cardiovascular System in Patients with Chronic Kidney Disease and Renal Transplant Recipients.
Cianciolo, G, Cappuccilli, M, Tondolo, F, Gasperoni, L, Zappulo, F, Barbuto, S, Iacovella, F, Conte, D, Capelli, I, La Manna, G
Nutrients. 2021;(5)
Abstract
Poor vitamin D status is common in patients with impaired renal function and represents one main component of the complex scenario of chronic kidney disease-mineral and bone disorder (CKD-MBD). Therapeutic and dietary efforts to limit the consequences of uremia-associated vitamin D deficiency are a current hot topic for researchers and clinicians in the nephrology area. Evidence indicates that the low levels of vitamin D in patients with CKD stage above 4 (GFR < 15 mL/min) have a multifactorial origin, mainly related to uremic malnutrition, namely impaired gastrointestinal absorption, dietary restrictions (low-protein and low-phosphate diets), and proteinuria. This condition is further worsened by the compromised response of CKD patients to high-dose cholecalciferol supplementation due to the defective activation of renal hydroxylation of vitamin D. Currently, the literature lacks large and interventional studies on the so-called non-calcemic activities of vitamin D and, above all, the modulation of renal and cardiovascular functions and immune response. Here, we review the current state of the art of the benefits of supplementation with native vitamin D in various clinical settings of nephrological interest: CKD, dialysis, and renal transplant, with a special focus on the effects on bone homeostasis and cardiovascular outcomes.
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Potential impact of the steroid hormone, vitamin D, on the vasculature.
Tintut, Y, Demer, LL
American heart journal. 2021;:147-153
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Abstract
The role of vitamin D in the cardiovascular system is complex because it regulates expression of genes involved in diverse metabolic processes. Although referred to as a vitamin, it is more accurately considered a steroid hormone, because it is produced endogenously in the presence of ultraviolet light. It occurs as a series of sequentially activated forms, here referred to as vitamin D-hormones. A little-known phenomenon, based on pre-clinical data, is that its biodistribution and potential effects on vascular disease likely depend on whether it is derived from diet or sunlight. Diet-derived vitamin D-hormones are carried in the blood, at least in part, in chylomicrons and lipoprotein particles, including low-density lipoprotein. Since low-density lipoprotein is known to accumulate in the artery wall and atherosclerotic plaque, diet-derived vitamin D-hormones may also collect there, and possibly promote the osteochondrogenic mineralization associated with plaque. Also, little known is the fact that the body stores vitamin D-hormones in adipose tissue with a half-life on the order of months, raising doubts about whether the use of the term "daily requirement" is appropriate. Cardiovascular effects of vitamin D-hormones are controversial, and risk appears to increase with both low and high blood levels. Since low serum vitamin D-hormone concentration is reportedly associated with increased cardiovascular and orthopedic risk, oral supplementation is widely used, often together with calcium supplements. However, meta-analyses show that oral vitamin D-hormone supplementation does not protect against cardiovascular events, findings that are also supported by a randomized controlled trial. These considerations suggest that prevalent recommendations for vitamin D-hormone supplementation for the purpose of cardiovascular protection should be carefully reconsidered.
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Cardiovascular Benefits of Extended-Time Nocturnal Hemodialysis.
Roumeliotis, A, Roumeliotis, S, Chan, C, Pierratos, A
Current vascular pharmacology. 2021;(1):21-33
Abstract
Hemodialysis (HD) remains the most utilized treatment for End-Stage Kidney Disease (ESKD) globally, mainly as conventional HD administered in 4 h sessions thrice weekly. Despite advances in HD delivery, patients with ESKD carry a heavy cardiovascular morbidity and mortality burden. This is associated with cardiac remodeling, left ventricular hypertrophy (LVH), myocardial stunning, hypertension, decreased heart rate variability, sleep apnea, coronary calcification and endothelial dysfunction. Therefore, intensive HD regimens closer to renal physiology were developed. They include longer, more frequent dialysis or both. Among them, Nocturnal Hemodialysis (NHD), carried out at night while asleep, provides efficient dialysis without excessive interference with daily activities. This regimen is closer to the physiology of the native kidneys. By providing increased clearance of small and middle molecular weight molecules, NHD can ameliorate uremic symptoms, control hyperphosphatemia and improve quality of life by allowing a liberal diet and free time during the day. Lastly, it improves reproductive biology leading to successful pregnancies. Conversion from conventional to NHD is followed by improved blood pressure control with fewer medications, regression of LVH, improved LV function, improved sleep apnea, and stabilization of coronary calcifications. These beneficial effects have been associated, among others, with better extracellular fluid volume control, improved endothelial- dependent vasodilation, decreased total peripheral resistance, decreased plasma norepinephrine levels and restoration of heart rate variability. Some of these effects represent improvements in outcomes used as surrogates of hard outcomes related to cardiovascular morbidity and mortality. In this review, we consider the cardiovascular effects of NHD.
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Role of Paraoxonase1 in the Regulation of High-Density Lipoprotein Functionality and in Cardiovascular Protection.
Khalil, A, Fulop, T, Berrougui, H
Antioxidants & redox signaling. 2021;(3):191-200
Abstract
Significance: Human paraoxonase (PON) is a member of the gene family that includes paraoxonase 1 (PON1), PON2, and PON3. PON is known for its capacity to hydrolyze a wide range of substrates, including organophosphorus compounds, nerve gases, and aromatic carboxylic acid esters. Recent Advances: Several studies have highlighted the involvement of PON, particularly PON1, in the modulation of the capacity of high-density lipoprotein (HDL) to protect against the atherosclerosis process and its clinical manifestations. PON1 exhibits antioxidant and anti-inflammatory activities and may be involved in the regulation of the principal antiatherogenic activity of HDL, that is, the regulation of the reverse cholesterol transport process. Critical Issues: Although epidemiological studies have shown that there is an inverse relationship between HDL levels and cardiovascular risk, several studies have emphasized the importance of HDL functionality in protecting against cardiovascular diseases (CVD). Given that PON1 is involved in several atheroprotective functions of HDL, the aim of this article is to review the existing literature on PON1 and to discuss the principal mechanisms by which PON1 may exert its different activities. Future Directions: The elucidation of the mechanisms by which PON1 modulates the functionality of HDL as well as the identification of the interventions that stimulate PON1 activity and/or increase its plasma concentration would make it possible to propose new strategies to prevent CVD. Antioxid. Redox Signal. 34, 191-200.
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Cardiovascular Effects of Energy Drinks in the Pediatric Population.
Moussa, M, Hansz, K, Rasmussen, M, Gillman, C, Pollard, C, Kwak, E, Izsak, E
Pediatric emergency care. 2021;(11):578-582
Abstract
Consumption of energy drinks in the pediatric population is correlated with more emergency department visits and causes adverse reactions, such as neurological, psychiatric, gastrointestinal, renal, and cardiovascular effects. These cardiovascular complications include increased cardiometabolic risk with high intake of sugar, short-term blood pressure increases and a decrease in cerebral blood flow due to the caffeine content, increased or decreased blood pressure from taurine, unmasked cardiac conditions, such as channelopathies, and atrial and ventral fibrillations. Cardiovascular complications can also arise when energy drinks are mixed with pharmaceutical drugs, such as amiodarone, potent CYP1A2 inhibitors, warfarin, digoxin, or corticosteroids. Combining energy drinks with alcohol also precipitates adverse cardiovascular events, posing a risk to the health of children and adolescents. This review further explores the ingredients in energy drinks and their mechanism of action in causing these cardiovascular complications.
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Cardiovascular Aging and Longevity: JACC State-of-the-Art Review.
Pietri, P, Stefanadis, C
Journal of the American College of Cardiology. 2021;(2):189-204
Abstract
Cardiovascular aging and longevity are interrelated through many pathophysiological mechanisms. Many factors that promote atherosclerotic cardiovascular disease are also implicated in the aging process and vice versa. Indeed, cardiometabolic disorders such as hyperglycemia, insulin resistance, dyslipidemia, and arterial hypertension share common pathophysiological mechanisms with aging and longevity. Moreover, genetic modulators of longevity have a significant impact on cardiovascular aging. The current knowledge of genetic, molecular, and biochemical pathways of aging may serve as a substrate to introduce interventions that might delay cardiovascular aging, thus approaching the goal of longevity. In the present review, the authors describe pathophysiological links between cardiovascular aging and longevity and translate these mechanisms into clinical data by reporting genetic, dietary, and environmental characteristics from long-living populations.
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Cardiovascular Disease in Patients with Chronic Obstructive Pulmonary Disease, Obstructive Sleep Apnoea Syndrome and Overlap Syndrome.
Voulgaris, A, Archontogeorgis, K, Steiropoulos, P, Papanas, N
Current vascular pharmacology. 2021;(3):285-300
Abstract
Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea syndrome (OSAS) are among the most prevalent chronic respiratory disorders. Accumulating data suggest that there is a significant burden of cardiovascular disease (CVD) in patients with COPD and OSAS, affecting negatively patients' quality of life and survival. Overlap syndrome (OS), i.e. the co-existence of both COPD and OSAS in the same patient, has an additional impact on the cardiovascular system multiplying the risk of morbidity and mortality. The underlying mechanisms for the development of CVD in patients with either OSAS or COPD and OS are not entirely elucidated. Several mechanisms, in addition to smoking and obesity, may be implicated, including systemic inflammation, increased sympathetic activity, oxidative stress and endothelial dysfunction. Early diagnosis and proper management of these patients might reduce cardiovascular risk and improve patients' survival. In this review, we summarize the current knowledge regarding epidemiological aspects, pathophysiological mechanisms and present point-to-point specific associations between COPD, OSAS, OS and components of CVD, namely, pulmonary hypertension, coronary artery disease, peripheral arterial disease and stroke.