Biomedical subjects

Rahul Garg

Publications and source records attributed to Rahul Garg.

6 recordsLinked to original sources

PubMed2005

Non-high-density lipoprotein cholesterol: why lower is better.

Recent comparative trials of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) suggest that lower is better and that reducing low-density lipoprotein cholesterol (LDL-C) levels to below 100 mg/dL can provide additional clinical benefit. Non-high-density lipoprotein cholesterol (non-HDL-C) contains more atherogenic cholesterol than LDL-C and is considered a more accurate measurement of the total amount of atherogenic particles in the circulation. Therefore, the principle that "lower is better" may also apply to lowering levels of non-HDL-C. In persons with high triglycerides (200-499 mg/dL), LDL-C remains the primary target of therapy, but non-HDL-C is an important secondary therapeutic target. Non-HDL-C is strongly correlated with small dense LDL as well as apolipoprotein B, an established predictor of cardiovascular disease risk. Current evidence indicates that statins not only rapidly and dramatically reduce LDL-C, but also have a similar effect on non-HDL-C, and that the greater the reduction in LDL-C, the greater will be the reduction in non-HDL-C.

Anticholesteremic Agents↗

PubMed2004

Aging-associated changes in cardiac gene expression.

Cardiovascular diseases (e.g., vascular diseases, strokes, heart failure) reach epidemic proportions in the elderly and are the primary limits to survival in man. Age-associated changes in heart structure and function represent the major risk factors in heart failure (HF) syndromes and are associated with altered patterns of gene expression that can generally be seen as relative changes in the abundance of gene transcripts. An understanding of the molecular mechanisms underlying these changes should be tantamount to defining a genetic basis for aging; however, the analysis of processes as complicated as aging requires an accounting of biological diversity. Until recently, most of the changes in transcript abundance were identified one at a time, but the advent of gene expression arrays has permitted rapid, large-scale expression profiling. This has provided information about the dynamics of total gene expression, which can be used to identify pathways and elucidate regulatory events that may be affected during senescence or in response to disease. Importantly, very large sample sizes or meta-analyses of studies of smaller sample sizes should be sufficient to account for the diversity of altered gene expression that directs alterations in specific molecular pathways, which underlie changes in cardiac structure and function in senescence and disease.

Aging↗

PubMed2004

The metabolic syndrome: what to treat, how to treat, what are the goals?

Metabolic syndrome is a cluster of risk factors for cardiovascular disease that include obesity, atherogenic dyslipidemia, raised blood pressure, and insulin resistance. The growing trend of obesity is associated with increased prevalence of metabolic syndrome. Optimizing diet and exercise are still the leading therapy for controlling the metabolic syndrome. Based on the current evidence, further emphasis should be placed on aggressive management of other metabolic risk factors such as high blood pressure and dyslipidemia.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

Sex- and age-dependent human transcriptome variability: implications for chronic heart failure.

Heart failure (HF) is the end result of progressive and diverse biological adaptations within the diseased myocardium. We used cDNA microarrays and quantitative PCR to examine the transcriptomes of 38 left ventricles from failing and nonfailing human myocardium. After identification of a pool of putative HF-responsive candidate genes by microarrays on seven nonfailing and eight failing hearts, we used quantitative PCR and a general linear statistical model in a larger sample set (n = 34) to validate and examine the role of contributing biological variables (age and sex). We find that most HF-candidate genes (transcription factors, Cebpb, Npat; signaling molecules, Map2k3, Map4k5; extracellular matrix proteins, Lum, Cola1; and metabolic enzymes, Mars) demonstrated significant changes in gene expression; however, the majority of differences among samples depended on variables such as sex and age, and not on HF alone. Some HF-responsive gene products also demonstrated highly significant changes in expression as a function of age and/or sex, but independent of HF (Ngp1, Cd163, and Npat). These results emphasize the need to account for biological variables (HF, sex and age interactions) to elucidate genomic correlates that trigger molecular pathways responsible for the progression of HF syndromes.

Adult↗

PubMed2002

Gene transfer of dominant-negative RhoA increases outflow facility in perfused human anterior segment cultures.

PURPOSE: To investigate the regulation of expression and the role of the RhoA gene in the human trabecular meshwork (TM). To attempt to modulate outflow facility by gene transfer of the RhoA gene's dominant-negative mutant protein. METHODS: Total RNA extracted from cultured human trabecular meshwork (HTM) cells treated with outflow facility drugs were analyzed by northern blot hybridization using an amplified human RhoA cDNA from plasmid pZip-RhoA wild type (wt) [1]. A dominant-negative form of RhoA (single amino acid substitution of Thr19 to Asn) was placed under the control of the CMV promoter and inserted into a replication-deficient adenoviral vector by overlapping recombination (AdhRhoA2). AdhRhoA2 was infected into perfused anterior segment cultures from post-mortem human donors and HTM and Schlemm's canal cells in culture. Changes in outflow facility (flow/pressure) were calculated as percent changes from baseline values (C0), pooled into treated and control groups and expressed as the mean plus minus standard error. HTM and Schlemm's Canal (SC) cells were fluorescently double-labeled for the RhoA protein and actin, paxillin, or ZO-1. RESULTS: Transcription of RhoA in HTM cells was not considerably affected by treatment of the cells with cytoskeletal/outflow facility drugs. At 66 h post-injection, anterior segments treated with AdhRhoA2 (n=9) exhibited an increase in outflow facility of 32.5 +/- 7.7% while that of the vehicle-injected controls (n=6) was 5.1 +/- 4.0% (p=0.02). HTM cells treated with AdhRhoA2 showed a marked change in morphology with a reduction in actin stress fibers and of the focal adhesion-containing protein, paxillin. Confluent monolayers of SC cells infected with AdhRhoA2 were devoid of peripheral ZO-1 staining indicating a loss of intercellular junctions. CONCLUSIONS: In the HTM cells, cytoskeletal/outflow facility drugs do not seem to affect the levels of RhoA mRNA, possibly suggesting the importance of mRNA availability to allow rapid turnover of its function. Gene transfer of inactive RhoA to the intact human TM results in an increase in outflow facility. This increase appears to be correlated with a loosening of the cell-substrate and cell-cell attachments in the cells of the outflow pathway. Adenoviral vectors carrying the dominant negative form of RhoA could potentially be utilized as a gene therapy to modulate outflow facility.

Actins↗

PubMed2002

Analysis of altered genomic expression profiles in the senescent and diseased myocardium using cDNA microarrays.

Cardiac function deteriorates with aging or disease. Short term, any changes in heart function may be beneficial, but long term the alterations are often detrimental. At a molecular level, functional adaptations involve quantitative and qualitative changes in gene expression. Analysis of all the RNA transcripts present in a cell's population (transcriptome) offers unprecedented opportunities to map these transitions. Microarrays (chips), capable of evaluating thousands of transcripts in one assay, are ideal for transcriptome analyses. Gene expression profiling provides information about the dynamics of total genome expression in response to environmental changes and may point to candidate genes responsible for the cascade of events that result in disease or are a consequence of aging. The aim of this review is to describe how comparisons of cellular transcriptomes by cDNA array based techniques provide information about the dynamics of total gene expression, and how the results can be applied to the study of cardiovascular disease and aging.

Cardiovascular Diseases↗