Nature Cardiovascular Research, Journal Year: 2024, Volume and Issue: 3(6), P. 637 - 650
Published: May 23, 2024
Language: Английский
Cell, Journal Year: 2024, Volume and Issue: 187(7), P. 1685 - 1700.e18
Published: March 1, 2024
Language: Английский
Citations
32
Circulation Research, Journal Year: 2024, Volume and Issue: 134(2), P. 226 - 244
Published: Jan. 18, 2024
The production and secretion of VLDLs (very-low-density lipoproteins) by hepatocytes has a direct impact on liver fat content, as well the concentrations cholesterol triglycerides in circulation thus affects both cardiovascular health, respectively. Importantly, insulin resistance, excess caloric intake, lack physical activity are associated with overproduction VLDL, hepatic steatosis, increased plasma levels atherogenic lipoproteins. Cholesterol remnant particles generated VLDL lipolysis risk factors for atherosclerotic disease have garnered increasing attention over last few decades. Presently, however, atherosclerosis is not only concern when considering today’s cardiometabolic patients, they often also experience prevalent disorder that can progress to steatohepatitis cirrhosis. This duality metabolic highlights importance understanding molecular regulation biogenesis lipoprotein transports out liver. Fortunately, there been resurgence interest intracellular assembly, trafficking, degradation, hepatocytes, which led many exciting new insights topic this review. Increasing our biology pathway will aid identification novel therapeutic targets improve health patients. review focuses, first time, duality.
Language: Английский
Citations
21
Lipids in Health and Disease, Journal Year: 2024, Volume and Issue: 23(1)
Published: Jan. 12, 2024
Abstract Reducing circulating lipid levels is the centerpiece of strategies for preventing and treating atherosclerotic cardiovascular disease (ASCVD). Despite many available lipid-lowering medications, a substantial residual risk remains. Current clinical guidelines focus on plasma low-density lipoprotein (LDL). Recent attention has been given to very (VLDL), precursor LDL, its role in development coronary atherosclerosis. Preclinical investigations have revealed that interventions targeting VLDL production or promoting metabolism, independent LDL receptor, can potentially decrease cholesterol provide therapeutic benefits. Currently, methods, such as mipomersen, lomitapide, ANGPTL3 inhibitors, are used reduce triglyceride by regulating lipidation, secretion, metabolism VLDL. Targeting represents an avenue new strategies. Interventions aimed at reducing enhancing hold promise lowering providing benefits beyond management ASCVD.
Language: Английский
Citations
15
Heliyon, Journal Year: 2025, Volume and Issue: 11(1), P. e41620 - e41620
Published: Jan. 1, 2025
Chronic kidney disease (CKD) is by far the most prevalent in world and now a major global public health problem because of increase diabetes, hypertension obesity. Traditional biomarkers function lack sensitivity specificity for early detection monitoring CKD progression, necessitating more sensitive diagnostic intervention. Dyslipidemia hallmark CKD. Advancements mass spectrometry (MS)-based lipidomics platforms have facilitated comprehensive analysis lipids biological samples revealed changes lipidome that are associated with metabolic disorders, which can be used as new diseases. It also critical discovery therapeutic targets drugs. In this article, we focus on CKD, methodologies their applications Additionally, introduce novel identified through approaches natural products derived from treatment We believe our study makes significant contribution to literature demonstrating improve lipidomic perspective.
Language: Английский
Citations
1
Cardiovascular Diabetology, Journal Year: 2025, Volume and Issue: 24(1)
Published: Jan. 8, 2025
Remnant cholesterol (remnant-C) contributes to atherosclerotic cardiovascular disease (ASCVD), particularly in individuals with impaired glucose metabolism. Patients metabolism and ASCVD remain at significant residual risk after coronary artery bypass grafting (CABG). However, the role of remnant-C this population has not yet been investigated. Adult patients prediabetes or diabetes undergoing isolated CABG were consecutively enrolled a longitudinal cohort between 2013 2018. The impact on short-term long-term outcomes was evaluated. included major perioperative complications. adverse cerebrovascular events (MACCEs). Remnant-C analyzed as both categorical continuous variable. Logistic regression, Cox restricted cubic spline analyses performed multivariate adjustments. In terms outcomes, elevated had higher incidence acute kidney injury (AKI) stage 2/3 (high vs. low remnant-C: 3.2% 2.4%; OR: 1.404, 95% CI 1.080-1.824). Each 1-standard deviation (SD) increase associated 16.6% AKI (OR: 1.160, 1.067-1.260). Long-term assessed median follow-up 3.2 years, during which 1,251 (9.3%) experienced MACCEs. 1-SD 6.6% MACCEs (HR: 1.066, 1.012-1.124), 7.1% all-cause death 1.071, 1.008-1.209), an 11.2% myocardial infarction 1.112, 1.011-1.222). These associations remained consistent when treated Importantly, association independent LDL-C levels; levels increased MACCE regardless whether ≤ 2.6 mmol/L > mmol/L. Subgroup analysis indicated that more pronounced insulin-treated patients. is CABG.
Language: Английский
Citations
1
Acta Physiologica, Journal Year: 2025, Volume and Issue: 241(2)
Published: Jan. 10, 2025
Abstract Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality globally, with elevated low‐density lipoprotein cholesterol (LDL‐C) levels being a major risk factor. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays critical role in regulating LDL‐C by promoting degradation hepatic receptors (LDLR) responsible for clearing from circulation. PCSK9 inhibitors novel lipid‐modifying agents that have demonstrated remarkable efficacy reducing plasma decreasing incidence CVD. However, broader clinical impacts functions beyond metabolism, including both desired undesired effects therapeutic inhibition, underscore urgent necessity to elucidate underlying mechanisms. Recent studies shown local vascular system can interact other such as CD36, LRP‐1, ABCA1. This provides new evidence supporting potential contribution CVD through LDLR‐independent signaling pathways. Therefore, this review aimed outline diverse on discuss mechanisms non‐cholesterol‐related processes, which will provide rational basis its long‐term pharmacological inhibition clinic.
Language: Английский
Citations
1
Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(7)
Published: March 27, 2025
ABSTRACT Background Within the tumor microenvironment, cells undergo metabolic reprogramming of cholesterol due to intrinsic cellular alterations and changes in extracellular milieu. Furthermore, within this microenvironment influences immune landscape tumors, facilitating evasion consequently promoting tumorigenesis. These biological involve modifications numerous enzymes associated with uptake synthesis, including NPC1L1, SREBP, HMGCR, SQLE, PCSK9. Review This review systematically summarizes role metabolism its cancer progression, examines mechanisms through which dysregulation affects discusses recent advancements therapies that target metabolism. Conclusion Targeting metabolism‐related can inhibit growth, reshape landscapes, rejuvenate antitumor immunity, offering potential therapeutic avenues treatment.
Language: Английский
Citations
1
npj Vaccines, Journal Year: 2023, Volume and Issue: 8(1)
Published: Sept. 28, 2023
Elevated low-density lipoprotein cholesterol (LDL-C) is an important risk factor in the development of atherosclerotic cardiovascular disease (ASCVD). Inhibitors proprotein convertase subtilisin/kexin type 9 (PCSK9), a negative regulator LDL-C metabolism, have emerged as promising approaches for reducing elevated levels. Here, we evaluated cholesterol-lowering efficacy virus-like particle (VLP) based vaccines that target epitopes found within LDL receptor (LDL-R) binding domain PCSK9. In both mice and non-human primates, bivalent VLP vaccine targeting two distinct on PCSK9 elicited strong durable antibody responses lowered macaques, single epitope was only effective at lowering levels combination with statins, whereas immunization without requiring statin co-administration. These data highlight alternative, vaccine-based approach LDL-C.
Language: Английский
Citations
21
Cardiovascular Research, Journal Year: 2024, Volume and Issue: 120(10), P. 1107 - 1125
Published: July 1, 2024
Abstract Nucleic acid-based therapies are being rapidly developed for prevention and management of cardiovascular diseases (CVD). Remarkable advancements have been achieved in the delivery, safety, effectiveness these therapeutics past decade. These can also modulate therapeutic targets that cannot be sufficiently addressed using traditional drugs or antibodies. Among nucleic acid-targeted under development CVD RNA-targeted approaches, including antisense oligonucleotides (ASO), small interfering RNAs (siRNA), novel genome editing techniques. Genetic studies identified potential suggested to play a causative role progression CVD. RNA- DNA-targeted particularly well delivered liver, where atherogenic lipoproteins angiotensinogen (AGT) produced. Current lipid metabolism include proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein A (ApoA), C3 (ApoC3), angiopoietin-like 3 (ANGPTL3). Several large-scale clinical programs way, which may attractive from therapy adherence point view, given long action therapeutics. In addition editing, concept gene transfer is presently assessment preclinical investigations as approach addressing low-density lipoprotein receptor deficiency. Furthermore, ongoing research exploring use treat arterial hypertension by reducing hepatic production. This review summarizes rapid translation siRNA ASO into dyslipidemia prevention. It outlines innovative options likely relevant future medicine.
Language: Английский
Citations
7
Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(17)
Published: Sept. 1, 2024
Abstract Cathepsin B (CTSB) is a member of the cysteine protease family, primarily responsible for degrading unnecessary organelles and proteins within acidic milieu lysosomes to facilitate recycling. Recent research has revealed that CTSB plays multifaceted role beyond its function as proteolytic enzyme in lysosomes. Importantly, recent data suggest significant impacts on different cardiac pathological conditions, such atherosclerosis (AS), myocardial infarction, hypertension, heart failure cardiomyopathy. Especially context AS, preclinical models clinical sample imaging indicate cathepsin activity‐based probe can reliably image activity foam cells atherosclerotic plaques; concurrently, it allows synchronous diagnostic therapeutic interventions. However, our knowledge cardiovascular disease still early stage. This paper aims provide comprehensive review significance physiology pathology, with objective laying theoretical groundwork development drugs targeting CTSB.
Language: Английский
Citations
6