Testosterone prescriptions have risen steadily and sharply in the USA despite a lack of clear understanding of the relationship between androgens and cardiovascular disease. In men with increasing age, testosterone levels decline and cardiovascular disease risk goes up. Ties between hypogonadism and cardiovascular disease are suggested by observational data, yet therapy with testosterone replacement has not been shown to mitigate that risk. To the contrary, recent literature has raised concern for increased cardiovascular disease in certain groups of men receiving testosterone therapy. In this article, we review current literature in an attempt to better understand what it suggests is the true relationship between testosterone and cardiovascular disease. We also take a closer look at effects of testosterone on lipids and HDL in particular, to see if this explains the cardiovascular effects seen in clinical studies.
Elevated post-prandial lipoprotein levels are common in patients with type 2 diabetes. Post-prandial lipoprotein alterations in type 2 diabetics are widely believed to drive inflammation and are considered a major risk factor for cardiovascular disease in diabetic patients. The incretins glucagon like peptide-1 (GLP-1) and glucose insulinotropic peptide (GIP) modulate post-prandial lipoproteins through a multitude of pathways that are independent of insulin and weight loss. Evidence from both animal models and humans seems to suggest an important effect on triglyceride rich lipoproteins (Apo48 containing) with little to no effects on other lipoproteins at least in humans. Dipeptidyl peptidase-4 (DPP4) inhibitors also appear to share these effects suggesting an important role for incretins in these effects. In this review, we will summarize lipid modulating effects of incretin analogs and DPP-4 inhibitors in both animal models and human studies and provide an overview of mechanisms responsible for these effects.
Despite wide use of statins, significant cardiovascular disease risk persists. High-density lipoprotein based therapy has not yielded any positive results in combating this disease. Newer methods to rapidly decrease plasma cholesterol are much needed. While apolipoprotein B is a ligand for low-density lipoprotein receptor, which clears low-density lipoprotein cholesterol in a highly regulated pathway, apolipoprotein E (apoE) is a ligand for clearing other apolipoprotein B containing atherogenic lipoproteins via an alternate receptor pathway, especially the heparin sulfate proteoglycans on the liver cell surface. We describe here a novel method that replaces apoE as a ligand to clear all of the atherogenic lipoproteins via the heparin sulfate proteoglycans pathway. This ligand replacement apoE mimetic peptide therapy, having been designated as an orphan drug by the US FDA, is in clinical trials.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：