Current Pharmaceutical Design - Volume 27, Issue 37, 2021

Patients who have achieved very low low-density lipoprotein CH (LDL-C) levels in clinical trials have shown the lowest cardio-vascular risk. The current clinical guidelines set such a concentration for LDL-C as < 1.4 mmol/L. However, the question of minimum permissible target values of the lipids remains unresolved. A number of experimental and clinical studies showed some unfavorable consequences of low LDL-C levels At the same time, the modern arsenal of lipid lowering drugs allows reducing LDL-C levels to extremely low values. This review presents an analysis of literature about the safety of low lipid spectrum parameters.

Cardiovascular diseases (CVDs) are a group of non-communicable disorders of the heart and blood vessels. Although lifestyle changes as well as pharmacological treatments and surgical interventions are available in many countries, CVDs are still considered the number one cause of mortality worldwide. Hence, considering that most CVDs are caused by genetic and environmental imbalances, micro-RNAs (miRNAs or miRs) appear as a plausible therapeutic option for CVDs as they are able to regulate a wide number of genes due to multiple target sites in different genes. Since miRNA-30 and -145 have been shown to play critical roles in the cardiovascular system, acting as important regulators of many functions and biological processes, this review focuses on summarizing recent findings on their involvement in CVDs, mainly as targets for therapeutic intervention. Therefore, the biology, mechanisms of action and data on what has been discovered so far regarding miRNA-30 and 145 as therapeutic targets for CVDs are presented.

CA125 is a well-known tumor marker for diagnosis, monitoring, and risk stratification in ovarian cancer. It is not specific for malignant tumors and may be elevated in benign disease. In the past two decades, increasing evidence has emerged suggesting that the plasma level of CA125 can serve as a novel surrogate of heart failure (HF). CA125 in patients with HF is synthesized by serous epithelial cells in response to both mechanical and inflammatory stimuli. In patients with HF, regardless of etiology, CA125 levels correlate with the severity of clinical, hemodynamic, and echocardiographic parameters and with other biomarkers. Elevated CA125 can identify patients at high risk of rehospitalization and mortality, whether short- or long-term. Serial measurements and combination with different pathophysiology biomarkers can provide a more accurate prognosis value. It also can guide treatment as a robust biomarker of fluid overload and inflammation, particularly for diuretic dose optimization. These properties make it a very promising candidate for risk stratification and treatment guidance of HF.

Cardiovascular disease (CVD) is a complex disease with multifactorial origin where cardiac membrane damage, inflammation, persistent oxidative stress, apoptosis and mitochondrial damage play a significant role. CVD is associated with high mortality rate and poor clinical outcome due to late diagnosis. Therefore, reliable accurate and specific biomarkers help in timely diagnosis and prevention of further damage. Beside creatine kinase-MB (CK-MB), cardiac troponin T (cTnT), brain natriuretic peptide (BNP), myeloperoxidase (MPO), etc. which are commonly used biomarkers, we need other supportive and accurate biomarkers for targeted diagnosis, as CVD is a complex diseased condition. Further, mechanism and symptoms of different types of CVD such as myocardial infarction, angina pectoris and heart failure are overlapping, hence in the recent time, multi-markers are used. Multi-markers include markers for oxidative stress, inflammation, apoptosis, membrane damage and energy metabolism. Understanding the etiology of disease, various novel markers have been developed and many of them are in pipeline. For bringing these biomarkers into clinical practice, various statistical criteria such as reclassification, discrimination and calibration are needed to validate and hence these novel biomarkers are yet to be used clinically. For pre-clinical studies, these markers play a vital role in establishing CVD and screening molecules for their cardio protective potential. We therefore, in the current manuscript have discussed various established and other important novel biomarkers for cardiovascular disorders, like biomarker for oxidative stress, cardiac inflammation, membrane damage, plaque rupture and thrombosis.

Red blood cell distribution width (RDW) is an inexpensive marker of anisocytosis easily available in the standard complete blood cell count. Besides its traditional use in the differential diagnosis of anemias, RDW values reflect abnormalities in erythropoiesis and red blood cell metabolism related to aging, sex, ethnicity, systemic inflammatory state, and oxidative stress. Thus, higher RDW values are common findings in several acute clinical conditions and chronic diseases. Increasing evidence suggests a prognostic role of higher RDW levels in many cardiovascular diseases. Among them, we aimed to review current literature focusing on the possible relation between RDW and atrial fibrillation (AF). Since aging, inflammation, and atrial substrate remodeling have a well-established role in AF pathogenesis, AF burden, and patient prognosis, we analyzed available data exploring the possible use of RDW in identifying patients at higher risk of AF and as a biomarker of worse outcomes for AF patients.

Cardiovascular diseases (CVD), primarily inflammatory cardiomyopathy, are characterized by the infiltration of inflammatory cells into the myocardium. It has a relatively high risk of deteriorating heart function and has heterogeneous etiologies. Inflammatory cardiomyopathy is mainly mediated by viral infections but can also be mediated by protozoa, fungal or bacterial infections. Besides that, there are a wide variety of drugs, toxic substances, and systemic immune-mediated diseases that result in the development of cardiovascular diseases (CVDs). Despite broad research, inflammatory cardiomyopathy has a poor prognosis. The roles of the pathogens, host genomic counterparts and environmental triggers in the progression of disease are still under consideration, including the role of some viruses as active inducers and others as bystanders. In this review article, we review the available evidence on the types, pathogenesis and treatment of myocarditis, inflammatory cardiomyopathy, and atherosclerosis with a particular focus on virus-associated cardiac diseases.

Obesity is a metabolic disease characterized by a chronic subclinical inflammatory response associated with an imbalance/dysregulation of cellular homeostasis in response to excessive nutrient intake and accumulation. CD4+ T-lymphocytes form different populations, Th1, Th2, Th9, Th17, Th22, and Treg cells, which have phenotypic and functional differences. Despite the active study of Th17 cells in severe disorders, their role in metabolic disorders, particularly in obesity, is not well understood. Th17 lymphocytes, depending on the microenvironment, can form pathogenic and nonpathogenic subpopulations. Systemic inflammation induces the reprogramming of the transcriptome of normal Th17 cells formed in epithelial tissues, which acquire new properties. A zone of overlapping states exists between IL-17A-producing cells, which does not allow a clear boundary between non-pathogenic Th17 and pathogenic Th17 lymphocytes. We assume that in obesity, the pool of inflammatory pathogenic Th17 cells with cytotoxic potential is a fraction of terminally differentiated memory lymphocytes which is responsible for developing autoimmune reactions.

The gut and brain are linked via various bidirectional pathways, and they communicate withand affect each other. The interaction between the gut-brain axis and the gut microbiota has attracted much attention in the development of hypertension. In this review, we have discussed the gut-brain-microbiota axis and its association with gut dysbiosis in terms of regulation of blood pressure using the autonomic nervous system, immune system, metabolites, hormones, and neurotransmitters. In addition, the treatments using microbiota that have been tried, to date, are briefly summarized. By understanding the mechanism by which gut-brainmicrobiota regulates blood pressure, the novel targets for hypertension treatment or a new therapeutic approach using the gut-brain-microbiota could be investigated.