In this issue of Cardiovascular & Hematological Disorders – Drug Targets, eight review articles are published with a
common theme of Atherosclerosis, Heart Disease and Diabetes. The surge of metabolic syndromes in the past 2-3 decades,
characterized by central obesity, hypertension, fasting hyperglycemia, and diabetic dyslipidemia, is associated with increasing
incidence of heart diseases and vascular complications. Clinically, prevention and treatment of metabolic syndromes and
related cardiovascular abnormalities necessitates a comprehensive understanding of alterations in cellular and molecular events
at transcriptional, post-transcriptional, and post-translational levels. The eight review articles published in this issue cover
research frontiers in the areas of histone methylation, cardiolipin metabolism, collagen homeostasis, energy utilization,
cholesterol movement, and lipoprotein production during the pathogenesis of cardiovascular complications and diabetic
Histone methylation represents an epigenetic mechanism underlying the pathophysiology of atherogenesis, hyperglycemia,
hypoxia, vascular inflammation, and cardiovascular diseases, such as congestive heart failure, dilated cardiomyopathy, and
thoracic aortic aneurysm. Xu and Fang have presented compelling experimental evidence, obtained from cell culture and
genetically modified animal models, that changes in histone methylation occur in cardiomyocytes and vasculature, composed of
vascular smooth muscle cells and endothelial cells. The authors foresee the development of new high-throughput technologies
enabling a comprehensive, genome-wide profiling of histone methylations between normal and diseased cardiovascular
Human congestive heart failure develops in association with hypertension, hyperinsulinemia, and diabetes. Hatch and coworkers
have reviewed the metabolism of cardiolipin, particularly tetralinoleoyl-cardiolipin, in the heart and the pathology of
the Barth Syndrome (BTHS) associated with deficiency of cardiolipin remodeling (i.e. transacylation) catalyzed by the BTHS
gene product tafazzin. The authors thus envisage that defining the mechanistic relationship, between acyl-chain composition of
cardiolipin, mitochondrial failure, and cardiomyopathy, may reveal new potential therapeutic targets for the prevention and
treatment of heart failure and cardiac dysfunction.
Another aspect of heart failure is the development of cardiac fibrosis, characterized by abnormal deposition of type I and
type III collagens. Roche and Czubryt have provided an overview of the current knowledge on transcriptional regulation of type
I collagen expression. The authors stressed the need for future investigations into the regulatory mechanisms (both
transcriptional and post-transcriptional/post-translational) that govern collagen homeostasis in different cell types in cardiac
tissue. A better characterization of fibrosis development at cellular and molecular levels will yield a better understanding of
other symptoms associated with metabolic disorders, such as fibrosis in nonalcoholic steatohepatitis.
From energy metabolism point of view, a switch from glucose utilization to fatty acid utilization by heart occurs under
diabetic conditions. The source of fatty acids is derived from (i) unsuppressed lipolysis in adipose tissue and (ii) hydrolysis of
plasma triglyceride-rich lipoproteins, such as very low-density lipoproteins (VLDL), catalyzed by lipoprotein lipase (LPL).
Rodrigues and co-workers reviewed experimental evidence for a concerted regulation of expression, transmigration, and
presentation of cardiac LPL on the endothelium surface in the coronary lumen. The augmented fatty acid utilization by
cardiomyocytes may constitute a cardiac protective mechanism during the early stages of hyperglycemia.
Fasting and postprandial dyslipidemia is a common feature of metabolic syndrome. Pharmaceutical means for the treatment
of dyslipidemia is aiming at reducing low density lipoprotein (LDL)-cholesterol and boosting high density lipoprotein (HDL)-
cholesterol. Adeli and co-workers presented a comprehensive overview on the current status of the use of dipeptidyl peptidase-
4 (DPP-4) inhibitors and the glucagon-like peptide-1 receptor (GLP-1R) agonists as potential therapy for dyslipidemia, in
addition to its known effect in treating hyperglycemia (as GLP-1 is a potent insulin secretagogue).
An additional complication in diabetic dyslipidemia is alterations in HDL structure and HDL composition, which apparently
exert a negative impact on the presumed anti-atherogenic function of HDL. Zheng and co-workers examined the impact of
changes in both HDL-protein (e.g. glycation of apoA-I) and HDL-lipids (e.g. elevation in triglyceride and sphingosine-1-
phosphate) on endothelium function under diabetic conditions, and explored the potential protective action of these changes at
early stage of hyperglycemia. Along the same line of HDL metabolism, Zhang and co-workers reviewed current understanding
concerning HDL biogenesis, emphasizing the requirement of ABCA1 and ABCG1 for apoA-I-containing HDL formation, and
the potential role of caveolin-1 in the process. In addition, Qin and co-workers presented experimental evidence suggesting a
possible involvement of phospholipid transfer protein (PLTP), a protein known to play a role in HDL remodeling, in the
process of diabetes and obesity development.
The eight topics presented in this issue are selected from panel presentations at The Second Canada-China Symposium on
Atherothrombosis, Diabetes and Obesity held at Simon Fraser University Harbour Centre on July 20-21, 2013. Ascardiovascular and metabolic diseases are becoming prevalent in both West and East demographics, the international science
community welcomes a strong participation of Chinese investigators joining the workforce in unraveling genetic and
environmental factors contributing to the pathogenesis of these debilitating chronic diseases.