Peroxisome proliferator-activated receptors (PPARs) are a group of ligand-binding transcription factors with pivotal action in regulating pleiotropic signaling pathways of energetic metabolism, immune responses and cell proliferation and differentiation. A significant body of evidence indicates that the PPARα receptor is an important modulator of plasma lipid and lipoprotein metabolism, with pluripotent effects influencing the lipid and apolipoprotein cargo of both atherogenic and antiatherogenic lipoproteins and their functionality. Clinical evidence supports an important role of PPARα agonists (fibric acid derivatives) in the treatment of hypertriglyceridemia and/or low high-density lipoprotein (HDL) cholesterol levels, although the effects of clinical trials are contradictory and point to a reduction in the risk of nonfatal and fatal myocardial infarction events. In this manuscript, we provide an up-to-date critical review of the existing relevant literature.

High-density lipoprotein (HDL) is an enigmatic member of the plasma lipid and lipoprotein transport system, best known for its ability to promote the reverse cholesterol efflux and the unloading of excess cholesterol from peripheral tissues. More recently, data in experimental mice and humans suggest that HDL may play important novel roles in other physiological processes associated with various metabolic disorders. Important parameters in the HDL functions are its apolipoprotein and lipid content, further reinforcing the principle that HDL structure defines its functionality. Thus, based on current evidence, low levels of HDL-cholesterol (HDL-C) or dysfunctional HDL particles contribute to the development of metabolic diseases such as morbid obesity, type 2 diabetes mellitus, and nonalcoholic fatty liver disease. Interestingly, low levels of HDL-C and dysfunctional HDL particles are observed in patients with multiple myeloma and other types of cancer. Therefore, adjusting HDL-C levels within the optimal range and improving HDL particle functionality is expected to benefit such pathological conditions. The failure of previous clinical trials testing various HDL-C-raising pharmaceuticals does not preclude a significant role for HDL in the treatment of atherosclerosis and related metabolic disorders. Those trials were designed on the principle of “the more the better”, ignoring the U-shape relationship between HDL-C levels and morbidity and mortality. Thus, many of these pharmaceuticals should be retested in appropriately designed clinical trials. Novel gene-editing-based pharmaceuticals aiming at altering the apolipoprotein composition of HDL are expected to revolutionize the treatment strategies, improving the functionality of dysfunctional HDL.

Background/Objectives: Lavender has been utilized for its medicinal properties since ancient times, with numerous health benefits reported. This study aimed to valorize solid waste from lavender essential oil production by developing a novel lavender extract from solid lavender residues. The extract’s preclinical safety and efficacy were evaluated with emphasis on plasma lipid and lipoprotein metabolism, glucose tolerance, and adipose tissue metabolic activity. Methods: Male C57BL/6 mice were divided into four groups of five mice each and fed for 30 days with lavender extract encapsulated in 10% maltodextrin, mixed with a standard chow diet. The first group (Lav 1×) received 21.1 mg/kg/day, the second group (Lav 10×) received 211 mg/kg/day, and the third group (Lav 100×) received 2110 mg/kg/day. A placebo group consumed the standard diet without lavender extract. Key outcomes included plasma lipid and lipoprotein profiles, transaminase levels, HDL antioxidant and anti-inflammatory potential, glucose tolerance, and mitochondrial activity in white (WAT) and brown (BAT) adipose tissues. Results: The novel lavender extract induced dose-dependent improvements in lipid and lipoprotein metabolism, glucose tolerance, and adipose tissue activity. The 2110 mg/kg dose (100×) demonstrated the most significant beneficial effects, although it was associated with a slight elevation in hepatic transaminase levels, indicating potential mild hepatic stress. Conclusions: Overall, the novel lavender extract exhibits promising health benefits with no major safety concerns at the tested doses, supporting its potential for therapeutic applications.

Despite major advances in lipid-lowering therapy and the widespread implementation of statins, ezetimibe, and PCSK9-targeted interventions, cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide. Intensive lowering of low-density lipoprotein cholesterol (LDL-C) has substantially reduced cardiovascular events; however, a considerable degree of residual cardiovascular risk persists even among patients achieving very low LDL-C levels. This observation has shifted contemporary cardiovascular research toward a broader understanding of atherosclerosis as a multifactorial disorder involving triglyceride-rich lipoproteins (TRLs), apolipoprotein B (APOB)-containing particles, dysfunctional high-density lipoproteins (HDLs), lipoprotein(a) [Lp(a)], endothelial dysfunction, and chronic vascular inflammation. Emerging evidence further suggests that psychological and behavioral factors, including specific personality traits and chronic psychosocial stress, may contribute independently to cardiovascular disease susceptibility and outcomes. The present review summarizes emerging risk factors associated with residual cardiovascular risk and highlights novel therapeutic strategies beyond LDL-C lowering. Collectively, current evidence supports a transition from a simplistic LDL-C-centric paradigm toward a multiple risk factor approach for atherosclerosis prevention and treatment.