Biomedicines 2022, 10, 1090. https://doi.org/10.3390/biomedicines10051090 www.mdpi.com/journal/biomedicines Review Targeted Strategy in Lipid-Lowering Therapy Ezgi Dayar and Olga Pechanova * Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Sienkiewiczova 1, 813 71 Bratislava, Slovakia; ezgi.dayar@savba.sk * Correspondence: olga.pechanova@savba.sk; Tel.: +421-911-938-910 Abstract: Dyslipidemia is characterized by a diminished lipid profile, including increased level of total cholesterol and low-density lipoprotein cholesterol (LDL-c) and reduced level of high-density lipoprotein cholesterol (HDL-c). Lipid-lowering agents represent an efficient tool for the prevention or reduction of progression of atherosclerosis, coronary heart diseases and metabolic syndrome. Statins, ezetimibe, and recently proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are the most effective and used drugs in clinical lipid-lowering therapy. These drugs are mainly aimed to lower cholesterol levels by different mechanisms of actions. Statins, the agents of the first-line therapy—known as 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors—suppress the liver cholesterol synthesis. Ezetimibe as the second-line therapy can decrease cholesterol by in- hibiting cholesterol absorption. Finally, the PCSK9 inhibitors act as an inducer of LDL excretion. In spite of their beneficial lipid-lowering properties, many patients suffer from their serious side ef- fects, route of administration, or unsatisfactory physicochemical characteristics. Clinical demand for dose reduction and the improvement of bioavailability as well as pharmacodynamic and pharma- cokinetic profile has resulted in the development of a new targeted therapy that includes nanopar- ticle carriers, emulsions or vaccination often associated with another more subtle form of admin- istration. Targeted therapy aims to exert a more potent drug profile with lipid-lowering properties either alone or in mutual combination to potentiate their beneficial effects. This review describes the most effective lipid-lowering drugs, their favorable and adverse effects, as well as targeted therapy and alternative treatments to help reduce or prevent atherosclerotic processes and cardiovascular events. Keywords: dyslipidemia; cholesterol; metabolic syndrome; statins; ezetimibe; PCSK9 inhibitors; nanoparticles; targeted therapy 1. Introduction Metabolic disorders are disorders that adversely affect the distribution of macronu- trients such as lipids, carbohydrates, and proteins. They are basically a consequence of abnormal chemical reactions in the body that alter the normal metabolic process. While congenital metabolic disorders are caused by genetic defects, acquired metabolic disor- ders are associated with external factors, such as an unhealthy lifestyle, little physical ac- tivity, and excessive caloric intake (for review see [1]). Eckel et al. (2010) documented that human lifestyle is associated with an inherited epigenetic pattern, which affects gene ex- pression, and protein activity that leads to the development of metabolic disorders [2]. Metabolic syndrome is the most common metabolic disorder and represents a cluster of conditions that occur together and increase the risk of heart disease, stroke, and type 2 diabetes. These conditions include increased blood pressure, high blood glucose, obesity, and dyslipidemia [3,4]. Dyslipidemia, manifested by elevated low-density lipoprotein cholesterol (LDL-c), is the primary cause of the development and progression of athero- sclerosis. Atherosclerosis is initiated by multiple interactions between oxidatively modi- fied lipids and lipoproteins, inflammatory factors, and components of the immune system Citation: Dayar, E.; Pechanova, O. Targeted Strategy in Lipid-Lowering Therapy. Biomedicines 2022, 10, 1090. https://doi.org/10.3390/ biomedicines10051090 Academic Editor: Anca Sima Received: 14 April 2022 Accepted: 3 May 2022 Published: 8 May 2022 Publisher’s Note: MDPI stays neu- tral with regard to jurisdictional claims in published maps and institu- tional affiliations. Copyright: © 2022 by the authors. Li- censee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and con- ditions of the Creative Commons At- tribution (CC BY) license (https://cre- ativecommons.org/licenses/by/4.0/).