Gold Nanoparticles Ameliorate Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Rats

The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data. Copyright 2001 Elsevier Science (USA).

Heart failure and related morbidity and mortality are increasing at an alarming rate, in large part, because of increases in aging, obesity, and diabetes mellitus. The clinical outcomes associated with heart failure are considerably worse for patients with diabetes mellitus than for those without diabetes mellitus. In people with diabetes mellitus, the presence of myocardial dysfunction in the absence of overt clinical coronary artery disease, valvular disease, and other conventional cardiovascular risk factors, such as hypertension and dyslipidemia, has led to the descriptive terminology, diabetic cardiomyopathy. The prevalence of diabetic cardiomyopathy is increasing in parallel with the increase in diabetes mellitus. Diabetic cardiomyopathy is initially characterized by myocardial fibrosis, dysfunctional remodeling, and associated diastolic dysfunction, later by systolic dysfunction, and eventually by clinical heart failure. Impaired cardiac insulin metabolic signaling, mitochondrial dysfunction, increases in oxidative stress, reduced nitric oxide bioavailability, elevations in advanced glycation end products and collagen-based cardiomyocyte and extracellular matrix stiffness, impaired mitochondrial and cardiomyocyte calcium handling, inflammation, renin-angiotensin-aldosterone system activation, cardiac autonomic neuropathy, endoplasmic reticulum stress, microvascular dysfunction, and a myriad of cardiac metabolic abnormalities have all been implicated in the development and progression of diabetic cardiomyopathy. Molecular mechanisms linked to the underlying pathophysiological changes include abnormalities in AMP-activated protein kinase, peroxisome proliferator-activated receptors, O-linked N-acetylglucosamine, protein kinase C, microRNA, and exosome pathways. The aim of this review is to provide a contemporary view of these instigators of diabetic cardiomyopathy, as well as mechanistically based strategies for the prevention and treatment of diabetic cardiomyopathy.

Fibroblasts comprise the largest cell population in the myocardium. In heart disease, the number of fibroblasts is increased either by replication of the resident myocardial fibroblasts, migration and transformation of circulating bone marrow cells, or by transformation of endothelial/epithelial cells into fibroblasts and myofibroblasts. The primary function of fibroblasts is to produce structural proteins that comprise the extracellular matrix (ECM). This can be a constructive process; however, hyperactivity of cardiac fibroblasts can result in excess production and deposition of ECM proteins in the myocardium, known as fibrosis, with adverse effects on cardiac structure and function. In addition to being the primary source of ECM proteins, fibroblasts produce a number of cytokines, peptides, and enzymes among which matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs), directly impact the ECM turnover and homeostasis. Function of fibroblasts can also in turn be regulated by MMPs and TIMPs. In this review article, we will focus on the function of cardiac fibroblasts in the context of ECM formation, homeostasis and remodeling in the heart. We will discuss the origins and multiple roles of cardiac fibroblasts in myocardial remodeling in different types of heart disease in patients and in animal models. We will further provide an overview of what we have learned from experimental animal models and genetically modified mice with altered expression of ECM regulatory proteins, MMPs and TIMPs.