scholarly journals Lipoprotein(a): An update on its role in human health and disease

2021 ◽  
Vol 12 (3) ◽  
pp. 92-102
Author(s):  
Amalia-Despoina Koutsogianni ◽  
Evangelos Liberopoulos ◽  
Alexandros D. Tselepis
Keyword(s):  
Cardiovascular Disease ◽  
Atherosclerotic Cardiovascular Disease ◽  
Main Question ◽  
Lipoprotein A ◽  
The Past ◽  
Causal Risk Factor ◽  
Potential Clinical Benefit ◽  
Pathophysiological Role ◽  
Health And Disease

Over the past few years, there has been an undiminished interest on lipoprotein(a) [Lp(a)]. High Lp(a) levels have been proposed as an independent causal risk factor for atherosclerotic cardiovascular disease (CVD). The main question that remains to be answered, however, is the potential clinical benefit of Lp(a) reduction. This will contribute to the enrichment of our knowledge on the exact pathophysiological role of this lipoprotein. This narrative review aims to summarize currently available data on the structure, metabolism, and pathogenicity of Lp(a).

scholarly journals Peroxiredoxins as Potential Targets for Cardiovascular Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1244
Author(s):  
Se-Jin Jeong ◽  
Jong-Gil Park ◽  
Goo Taeg Oh
Keyword(s):  
Cardiovascular Disease ◽  
Intracellular Signaling ◽  
Toxic Substance ◽  
Regulatory Proteins ◽  
The Past ◽  
Glutathione Peroxidases ◽  
Intracellular Signals ◽  
Common Etiology ◽  
Cardiovascular Cells

Increased oxidative stress (OS) is considered a common etiology in the pathogenesis of cardiovascular disease (CVD). Therefore, the precise regulation of reactive oxygen species (ROS) in cardiovascular cells is essential to maintain normal physiological functions. Numerous regulators of cellular homeostasis are reportedly influenced by ROS. Hydrogen peroxide (H2O2), as an endogenous ROS in aerobic cells, is a toxic substance that can induce OS. However, many studies conducted over the past two decades have provided substantial evidence that H2O2 acts as a diffusible intracellular signaling messenger. Antioxidant enzymes, including superoxide dismutases, catalase, glutathione peroxidases, and peroxiredoxins (Prdxs), maintain the balance of ROS levels against augmentation of ROS production during the pathogenesis of CVD. Especially, Prdxs are regulatory sensors of transduced intracellular signals. The intracellular abundance of Prdxs that specifically react with H2O2 act as regulatory proteins. In this review, we focus on the role of Prdxs in the regulation of ROS-induced pathological changes in the development of CVD.

Role of coronary artery calcium score in the primary prevention of cardiovascular disease

BMJ ◽  
2021 ◽  
pp. n776
Author(s):  
Khurram Nasir ◽  
Miguel Cainzos-Achirica
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery ◽  
Primary Prevention ◽  
Coronary Artery Calcium ◽  
Calcium Score ◽  
Coronary Plaque ◽  
Preventive Therapy ◽  
Atherosclerotic Cardiovascular Disease ◽  
International Studies

Abstract First developed in 1990, the Agatston coronary artery calcium (CAC) score is an international guideline-endorsed decision aid for further risk assessment and personalized management in the primary prevention of atherosclerotic cardiovascular disease. This review discusses key international studies that have informed this 30 year journey, from an initial coronary plaque screening paradigm to its current role informing personalized shared decision making. Special attention is paid to the prognostic value of a CAC score of zero (the so called “power of zero”), which, in a context of low estimated risk thresholds for the consideration of preventive therapy with statins in current guidelines, may be used to de-risk individuals and thereby inform the safe delay or avoidance of certain preventive therapies. We also evaluate current recommendations for CAC scoring in clinical practice guidelines around the world, and past and prevailing barriers for its use in routine patient care. Finally, we discuss emerging approaches in this field, with a focus on the potential role of CAC informing not only the personalized allocation of statins and aspirin in the general population, but also of other risk-reduction therapies in special populations, such as individuals with diabetes and people with severe hypercholesterolemia.

scholarly journals Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease: A Scientific Statement From the American Heart Association

2021 ◽  
Author(s):  
Gissette Reyes-Soffer ◽  
Henry N. Ginsberg ◽  
Lars Berglund ◽  
P. Barton Duell ◽  
Sean P. Heffron ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Risk Factor ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Density Lipoprotein ◽  
Major Protein ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipoprotein A ◽  
Scientific Statement ◽  
Genetically Determined

High levels of lipoprotein(a) [Lp(a)], an apoB100-containing lipoprotein, are an independent and causal risk factor for atherosclerotic cardiovascular diseases through mechanisms associated with increased atherogenesis, inflammation, and thrombosis. Lp(a) is predominantly a monogenic cardiovascular risk determinant, with ≈70% to ≥90% of interindividual heterogeneity in levels being genetically determined. The 2 major protein components of Lp(a) particles are apoB100 and apolipoprotein(a). Lp(a) remains a risk factor for cardiovascular disease development even in the setting of effective reduction of plasma low-density lipoprotein cholesterol and apoB100. Despite its demonstrated contribution to atherosclerotic cardiovascular disease burden, we presently lack standardization and harmonization of assays, universal guidelines for diagnosing and providing risk assessment, and targeted treatments to lower Lp(a). There is a clinical need to understand the genetic and biological basis for variation in Lp(a) levels and its relationship to disease in different ancestry groups. This scientific statement capitalizes on the expertise of a diverse basic science and clinical workgroup to highlight the history, biology, pathophysiology, and emerging clinical evidence in the Lp(a) field. Herein, we address key knowledge gaps and future directions required to mitigate the atherosclerotic cardiovascular disease risk attributable to elevated Lp(a) levels.

scholarly journals Regulatory Role of N6-methyladenosine (m6A) Modification in Osteosarcoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Yujie Zhang ◽  
Yanyan Wang ◽  
Liwei Ying ◽  
Sifeng Tao ◽  
Mingmin Shi ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Research Trends ◽  
Rna Modification ◽  
Future Research ◽  
Related Factors ◽  
The Past ◽  
Pathophysiological Role ◽  
Primary Bone ◽  
Non Coding Rnas

Osteosarcoma is the most common primary bone malignancy, typically occurring in childhood or adolescence. Unfortunately, the clinical outcomes of patients with osteosarcoma are usually poor because of the aggressive nature of this disease and few treatment advances in the past four decades. N6-methyladenosine (m6A) is one of the most extensive forms of RNA modification in eukaryotes found both in coding and non-coding RNAs. Accumulating evidence suggests that m6A-related factors are dysregulated in multiple osteosarcoma processes. In this review, we highlight m6A modification implicated in osteosarcoma, describing its pathophysiological role and molecular mechanism, as well as future research trends and potential clinical application in osteosarcoma.

scholarly journals Lp(a) (Lipoprotein[a]) Concentrations and Incident Atherosclerotic Cardiovascular Disease

2020 ◽  
Author(s):  
Aniruddh P. Patel ◽  
Minxian Wang ◽  
James P. Pirruccello ◽  
Patrick T. Ellinor ◽  
Kenney Ng ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
South Asian ◽  
Clinical Importance ◽  
Atherosclerotic Cardiovascular Disease ◽  
Middle Aged ◽  
Lipoprotein A ◽  
Hazard Ratios ◽  
Middle Aged Adults ◽  
Relationship Of

Objective: Lipoprotein(a) concentrations are associated with atherosclerotic cardiovascular disease (ASCVD), and new therapies that enable potent and specific reduction are in development. In the largest study conducted to date, we address 3 areas of uncertainty: (1) the magnitude and shape of ASCVD risk conferred across the distribution of lipoprotein(a) concentrations; (2) variation of risk across racial and clinical subgroups; (3) clinical importance of a high lipoprotein(a) threshold to guide therapy. Approach and Results: Relationship of lipoprotein(a) to incident ASCVD studied in 460 506 middle-aged UK Biobank participants. Over a median follow-up of 11.2 years, incident ASCVD occurred in 22 401 (4.9%) participants. Median lipoprotein(a) concentration was 19.6 nmol/L (25th–75th percentile 7.6–74.8). The relationship between lipoprotein(a) and ASCVD appeared linear across the distribution, with a hazard ratio of 1.11 (95% CI, 1.10–1.12) per 50 nmol/L increment. Substantial differences in concentrations were noted according to race—median values for white, South Asian, black, and Chinese individuals were 19, 31, 75, and 16 nmol/L, respectively. However, risk per 50 nmol/L appeared similar—hazard ratios of 1.11, 1.10, and 1.07 for white, South Asian, and black individuals, respectively. A high lipoprotein(a) concentration defined as ≥150 nmol/L was present in 12.2% of those without and 20.3% of those with preexisting ASCVD and associated with hazard ratios of 1.50 (95% CI, 1.44–1.56) and 1.16 (95% CI, 1.05–1.27), respectively. Conclusions: Lipoprotein(a) concentrations predict incident ASCVD among middle-aged adults within primary and secondary prevention contexts, with a linear risk gradient across the distribution. Concentrations are variable across racial subgroups, but the associated risk appears similar.

scholarly journals Arginine Derivatives in Cerebrovascular Diseases: Mechanisms and Clinical Implications

2020 ◽  
Vol 21 (5) ◽  
pp. 1798 ◽  
Author(s):  
Gerrit M. Grosse ◽  
Edzard Schwedhelm ◽  
Hans Worthmann ◽  
Chi-un Choe
Keyword(s):  
Ischemic Stroke ◽  
Vascular Function ◽  
Cerebrovascular Diseases ◽  
Current Evidence ◽  
Clinical Implications ◽  
Pathophysiological Role ◽  
Health And Disease ◽  
Oxide Synthase ◽  
Derivatives Of

The amino acid L-arginine serves as substrate for the nitric oxide synthase which is crucial in vascular function and disease. Derivatives of arginine, such as asymmetric (ADMA) and symmetric dimethylarginine (SDMA), are regarded as markers of endothelial dysfunction and have been implicated in vascular disorders. While there is a variety of studies consolidating ADMA as biomarker of cerebrovascular risk, morbidity and mortality, SDMA is currently emerging as an interesting metabolite with distinct characteristics in ischemic stroke. In contrast to dimethylarginines, homoarginine is inversely associated with adverse events and mortality in cerebrovascular diseases and might constitute a modifiable protective risk factor. This review aims to provide an overview of the current evidence for the pathophysiological role of arginine derivatives in cerebrovascular ischemic diseases. We discuss the complex mechanisms of arginine metabolism in health and disease and its potential clinical implications in diverse aspects of ischemic stroke.

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