There is a huge number of noncoding RNA (ncRNA) transcripts in the cell with important roles in modulation of different mechanisms. ANRIL is a long ncRNA with 3.8 kb length that is transcribed in the opposite direction of the INK4/ARF locus in chromosome 9p21. It was shown that polymorphisms within this locus are associated with vascular disorders, notably coronary artery disease (CAD), which is considered as a risk factor for life-threatening events like myocardial infarction and stroke. ANRIL is subjected to a variety of splicing patterns producing multiple isoforms. Linear isoforms could be further transformed into circular ones by back-splicing. ANRIL regulates genes in atherogenic network in a positive or negative manner. This regulation is implemented both locally and remotely. While CAD is known as a proliferative disorder and cell proliferation plays a crucial role in the progression of atherosclerosis, the functions of ANRIL and CAD development are intertwined remarkably. This makes ANRIL a suitable target for diagnostic, prognostic, and even therapeutic aims. In this review, we tried to present a comprehensive appraisal on different aspects of ANRIL including its location, structure, isoforms, expression, and functions. In each step, the contribution of ANRIL to atherosclerosis is discussed.

Coronary artery disease has remained a major health challenge despite enormous progress in prevention, diagnosis, and treatment strategies. Formation of atherosclerotic plaque is a chronic process that is developmentally influenced by intrinsic and extrinsic determinants. Inflammation triggers atherosclerosis, and the fundamental element of inflammation is the immune system. The immune system involves in the atherosclerosis process by a variety of immune cells and a cocktail of mediators. It is believed that almost all main components of this system possess a profound contribution to the atherosclerosis. However, they play contradictory roles, either protective or progressive, in different stages of atherosclerosis progression. It is evident that monocytes are the first immune cells appeared in the atherosclerotic lesion. With the plaque growth, other types of the immune cells such as mast cells, and T lymphocytes are gradually involved. Each cell releases several cytokines which cause the recruitment of other immune cells to the lesion site. This is followed by affecting the expression of other cytokines as well as altering certain signaling pathways. All in all, a mix of intertwined interactions determine the final outcome in terms of mild or severe manifestations, either clinical or subclinical. Therefore, it is of utmost importance to precisely understand the kind and degree of contribution which is made by each immune component in order to stop the growing burden of cardiovascular morbidity and mortality. In this review, we present a comprehensive appraisal on the role of immune cells in the atherosclerosis initiation and development.

CD4 + T-lymphocyte counts are used to assess CD4 + decline and the stage of human immunodeficiency virus (HIV) progression in HIV-infected patients. Clinical observation suggests that HIV progress more rapid in females than males. Of the original 5000 HIV-infected population of Western New York HIV/AIDS, Referral Center at Erie County Medical Center (ECMC), 1422 participated in the cohort study. We identified 333 HIV-infected patients with CD4 + T-cell-counts ≥ 500/µƖ, among them 178 met the inclusion criteria for the 10-year study. Females had higher mode (600 vs. 540) and mean (741.9 vs. 712.2) CD4 + counts than males at baseline. However, CD4 + declined faster among females in a shorter time than males (234.5 vs. 158.6, P < 0.004), with rapid HIV progression. Univariate analyses determined that females had a 40% higher risk for CD4 + decline than males. The bivariate analyses specified CD4 + decline remained greater in females than males. Multivariate analyses which employed Cox’s proportional Hazard-Model to adjust for numerous variables simultaneously identified women had almost twice the risk for CD4 + decline and rapid HIV progression than males (RR = 1.93; 95%CI 1.24, 2.99). Although the biological mechanism remains unknown, findings suggest gender differences in CD4 + decline, with a higher risk of rapid HIV progression and shorter longevity in females.

To determine the conclusive integrity in the Shiraz Cohort Heart Study (SCHS) project, management began quality assurance (QA) and quality control (QC) of the collected data throughout the study end-points. The QA is a focused process that prevents and detects data collection errors and verification of intended requirements in the SCHS. The QC is a subset of QA intended to capture errors in processing data through testing and preventive processes to identify problems, defects, or intended requirements. SCHS involved 10,000 males and females aged 40-70 over a 10-year follow-up period with cardiovascular diseases (CVDs) in the city of Shiraz, Iran. The study measured events and access to preventive care in Shiraz city. The SCHS identified unique barriers to select national study models in developing standardized measures related to variations in ethnicity, religion, cross-cultural considerations, and others. A suggested response to this problem was to develop a mechanism to standardize elements of the questionnaire, study design, and method of administration. This action was based on the geographically normal distribution of the Family Physician Health and Medical Services in Shiraz. Important QA and QC decisions were developed and adopted in the construction of the SCHS and follow-up to ensure conclusive integrity.

Atherosclerotic lesions of the coronary arteries are still in charge of significant annual morbidity and mortality despite intense therapeutic advancements. Genome-born elements contribute substantially to the atherosclerosis process. ANRIL is one of the long non-coding RNAs with outstanding functions particularly regulation of genes involved in atherosclerosis development. In this study, we measured ANRIL expression (circular-, linear-, and circular/linear ratio) in hypertensive patients with coronary artery disease (CAD) compared with peers without CAD. Among hypertensive patients who were candidates of angiography, 25 subjects with CAD and the equal number without CAD were considered as the case and control groups, respectively. Different categories of data were recorded through a predefined questionnaire. Before angiography, blood samples were obtained. After RNA extraction and cDNA synthesis, quantitative PCR was performed using specific primers for circular and linear ANRIL. Age and gender were not different between the groups. Most of the parameters of the lipid profile besides creatinine and blood urea nitrogen were remarkably worse in the case group. Circular ANRIL was significantly lower in the case group while linear counterparts were significantly higher in this group. Circular/linear ratio was also significantly lower in the case group. To overcome growing devastating trend of CAD, scrutinizing different factors involved in the initiation and development of atherosclerosis is a must. Atheroprotective role of circular ANRIL and atheroprogressive role of linear ANRIL were shown in our patients with hypertension.