Transcriptomic therapy for dyslipidemias utilizing nucleic acids targeted at ANGPTL3

Angiopoietin-like protein 3 (ANGPTL3) is a key physiological regulator of plasma lipid and lipoprotein metabolism that involves the control of enzymes, lipoprotein and endothelial lipases. Inhibition of ANGPTL3 offers a new approach for correcting the health risks of dyslipidemia, including familial hypercholesterolemia, mixed hyperlipidemia, metabolic syndrome and/or severe hypertriglyceridemia. ANGPTL3 inhibition with nucleic acid-based antisense oligonucleotide and siRNA can correct dyslipidemia chiefly by reducing production and increasing catabolism of triglyceride-rich lipoprotein and LDL particles. Early clinical trials have demonstrated that these agents can safely and effectively lower plasma triglyceride and LDL-cholesterol levels by up to 70 and 50%, respectively. However, the long-term safety and cost–effectiveness of these agents await to be confirmed in an ongoing and future clinical trials.

Rosuvastatin and Fenofibrate Combination in The Treatment of Mixed Hyperlipidemia: A Narrative Review

Introduction: Patients with mixed dyslipidemia are presented with high levels of low-density lipid cholesterol (LDL-C), triglycerides (TG), and reduced high-density lipid cholesterol (HDL-C). Though useful in lowering LDL-C, therapy with rosuvastatin is insufficient in optimizing the overall lipid profile, thus putting the patient at risk of residual cardiovascular risk. A combination of statin with other lipid-modifying agents has been used with more efficient lipid control and cardiovascular risk prevention. Of these, fenofibric acid is the most frequently used, along with rosuvastatin. Methods: Authors conducted a literature search of published literature to assess the use of rosuvastatin and fenofibrate combination in the management of mixed hyperlipidaemia. Results and discussion: The authors selected a total of 46 articles to be included in the review. Due to the small number of articles and heterogeneity on the combination of rosuvastatin and fenofibrate combination in mixed hyperlipidemia, the findings herein are presented using narrative summaries. Based on the thorough assessment of the selected literature, the essential themes that emerged from the review include safety and efficacy of rosuvastatin and fenofibrate combination, place of therapy of rosuvastatin, and fenofibrate combination, and potential cardiovascular risk reduction with rosuvastatin and fenofibrate combination. Conclusion: Based on the review, the authors suggested that the combination therapy with fenofibric acid was beneficial, well-tolerated with a similar safety profile compared with statin monotherapy. The combination therapy of moderate dose rosuvastatin and fenofibric acid led to a reduction of cardiovascular risk factors via several pathways.

Evaluation of the frequency of fasting and postprandial hyperlipidemia in healthy Schnauzers and of hepatic changes and insulin resistance in hyperlipidemic Schnauzers

Hyperlipidemia in dogs can be primary or secondary. Secondary hyperlipidemia is the most frequent form, and it is associated to endocrine disorders, obesity, and glucocorticoid therapy. Primary hypertriglyceridemia of Miniature Schnauzers is a well-known condition and may predispose to the development of pancreatitis, diabetes, liver and neurological disorders. The goal of this study was to identify the prevalence of hyperlipidemia in 55 asymptomatic Miniature Schnauzers, and the frequency of hepatic changes and insulin resistance in hyperlipidemic dogs. Of the 55 dogs in the study, 56.4% had primary hyperlipidemia. In 23.6% of these cases, the hyperlipidemia was characterized by isolated hypertriglyceridemia, while isolated hypercholesterolemia was present in 20% of the cases. Mixed hyperlipidemia was observed in 12.7% of hyperlipidemic dogs. Hypertriglyceridemia was considered mild in 21/8% of the cases, and moderate to severe in 14.5% of them. Serum ALT was elevated in 32.3% of hyperlipidemic dogs and serum AF was elevated in 38.7% of the cases. Insulin resistance was observed in 90.3% of hyperlipidemic dogs. Given the high prevalence of hyperlipidemia in our sample, and the observed metabolic changes in hyperlipidemic dogs, we suggest that all Miniature Schnauzers are screened for hyperlipidemia as an aid to early diagnosis of this disorder and prevention of complications.