👤 Theodosios D Filippatos

Psoriasis is a chronic inflammatory condition related to an increased atherosclerotic cardiovascular disease (ASCVD) risk. To investigate whether lipoprotein (a) [Lp(a)] levels are increased in patients with psoriasis. A comprehensive literature search up to January 30, 2025 was conducted utilizing PubMed and Cochrane Library databases. A qualitative synthesis and a meta-analysis on Lp(a) mean differences (MD) between psoriasis cases and healthy controls (HC) was performed. The protocol of this meta-analysis has been registered to PROSPERO (No. CRD420250652465). Eighteen studies with 1650 psoriasis patients and 1621 HC were eligible for qualitative synthesis. Pooled analysis from 16 studies (1401 psoriasis patients and 1320 HC) demonstrated that psoriasis patients had significantly higher Lp(a) levels compared with the HC group (MD: 6.72 mg/dL, 95%CI: 4.32-9.12, Our findings suggest that Lp(a) levels are significantly elevated in psoriasis patients, further adding to their ASCVD risk. Show less

Despite significant progress in plasma lipid lowering strategies, recent clinical trials highlight the existence of residual cardiovascular risk. Angiopoietin-like protein 3 (ANGPTL3) and apolipoprotein C-III (Apo C-III) have been identified as novel lipid-lowering targets. Apo C-III and ANGPTL3 have emerged as novel regulators of triglyceride (TG) and low-density lipoprotein-cholesterol (LDL-C) levels. ANGPTL3 is an inhibitor of lipoprotein lipase (LPL), reducing lipolysis of Apo B-containing lipoproteins. Loss-of-function ANGPLT3 mutations are associated with reduced plasma cholesterol and TG, while novel ANGPLT3 inhibition strategies, including monoclonal antibodies (evinacumab), ANGPLT3 antisense oligonucleotides (IONIS-ANGPTL3-L Show less

Angiopoietin-like 3 (ANGPTL3) is a regulator of plasma triglyceride (TRG) levels due to its inhibitory action on the activity of lipoprotein lipase (LPL). ANGPTL3 is proteolytically cleaved by proprotein convertases to generate an active N-terminal domain, which forms a complex with ANGPTL8 orchestrating LPL inhibition. ANGPTL3-4-8 mouse model studies indicate that these three ANGPTL family members play a significant role in partitioning the circulating TRG to specific tissues according to nutritional states. Recent data indicate a positive correlation of ANGPTL3 with plasma glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) in insulin-resistant states. The aim of this review is to critically present the metabolic effects of ANGPTL3, focusing on the possible mechanisms involved in the dysregulation of carbohydrate homeostasis by this protein. Heterozygous and homozygous carriers of ANGPTL3 loss-of-function mutations have reduced risk for type 2 diabetes mellitus. Suggested mechanisms for the implication of ANGPTL3 in carbohydrate metabolism include the (i) increment of free fatty acids (FFAs) owing to the enhancement of lipolysis in adipose tissue, which can induce peripheral as well as hepatic insulin resistance; (ii) promotion of FFA flux to white adipose tissue during feeding, leading to the attenuation of de novo lipogenesis and decreased glucose uptake and insulin sensitivity; (iii) induction of hypothalamic LPL activity in mice, which is highly expressed throughout the brain and is associated with enhanced brain lipid sensing, reduction of food intake, and inhibition of glucose production (however, the effects of ANGPTL3 on hypothalamic LPL in humans need more clarification); and (iv) upregulation of ANGPTL4 expression (owing to the plasma FFA increase), which possibly enhances insulin resistance due to the selective inhibition of LPL in white adipose tissue leading to ectopic lipid accumulation and insulin resistance. Future trials will reveal if ANGPTL3 inhibition could be considered an alternative therapeutic target for dyslipidemia and dysglycemia. Show less

Cholesteryl ester transfer protein (CETP) inhibitors significantly increase serum high-density lipoprotein cholesterol (HDL) cholesterol levels and decrease low-density lipoprotein cholesterol (LDL) cholesterol concentration. However, three drugs of this class failed to show a decrease of cardiovascular events in high-risk patients. A new CETP inhibitor, anacetrapib, substantially increases HDL cholesterol and apolipoprotein (Apo) AI levels with a profound increase of large HDL2 particles, but also pre-β HDL particles, decreases LDL cholesterol levels mainly due to increased catabolism of LDL particles through LDL receptors, decreases lipoprotein a (Lp(a)) levels owing to a decreased Apo (a) production and, finally, decreases modestly triglyceride (TRG) levels due to increased lipolysis and increased receptor-mediated catabolism of TRG-rich particles. Interestingly, anacetrapib may be associated with a beneficial effect on carbohydrate homeostasis. Furthermore, the Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification (REVEAL) trial showed that anacetrapib administration on top of statin treatment significantly reduces cardiovascular events in patients with atherosclerotic vascular disease without any significant increase of adverse events despite its long half-life. Thus, anacetrapib could be useful for the effective management of dyslipidemias in high-risk patients that do not attain their LDL cholesterol target or are statin intolerable, while its role in patients with increased Lp(a) levels remains to be established. Show less