Uncovering the link between diabetes and cardiovascular diseases: insights from adipose-derived stem cells.

Cardiovascular diseases (CVDs) are the leading causes of morbidity and mortality worldwide. The escalating global occurrence of obesity and diabetes mellitus (DM) has led to a significant upsurge in individuals afflicted with CVDs. As the prevalence of CVDs continues to rise, it is becoming increasingly important to identify the underlying cellular and molecular mechanisms that contribute to their development and progression, which will help discover novel therapeutic avenues. Adipose tissue (AT) is a connective tissue that plays a crucial role in maintaining lipid and glucose homeostasis. However, when AT is exposed to diseased conditions, such as DM, this tissue will alter its phenotype to become dysfunctional. AT is now recognized as a critical contributor to CVDs, especially in patients with DM. AT is comprised of a heterogeneous cellular population, which includes adipose-derived stem cells (ADSCs). ADSCs resident in AT are believed to regulate physiological cardiac function and have potential cardioprotective roles. However, recent studies have also shown that ADSCs from various adipose tissue depots become pro-apoptotic, pro-inflammatory, less angiogenic, and lose their ability to differentiate into various cell lineages upon exposure to diabetic conditions. This review aims to summarize the current understanding of the physiological roles of ADSCs, the impact of DM on ADSC phenotypic changes, and how these alterations may contribute to the pathogenesis of CVDs.

Attenuation of Smooth Muscle Cell Phenotypic Switching by Angiotensin 1-7 Protects against Thoracic Aortic Aneurysm.

Thoracic aortic aneurysm (TAA) involves extracellular matrix (ECM) remodeling of the aortic wall, leading to reduced biomechanical support with risk of aortic dissection and rupture. Activation of the renin-angiotensin system, and resultant angiotensin (Ang) II synthesis, is critically involved in the onset and progression of TAA. The current study investigated the effects of angiotensin (Ang) 1-7 on a murine model of TAA. Male 8-10-week-old ApoEKO mice were infused with Ang II (1.44 mg/kg/day) and treated with Ang 1-7 (0.576 mg/kg/day). ApoEKO mice developed advanced TAA in response to four weeks of Ang II infusion. Echocardiographic and histological analyses demonstrated increased aortic dilatation, excessive structural remodelling, perivascular fibrosis, and inflammation in the thoracic aorta. Ang 1-7 infusion led to attenuation of pathological phenotypic alterations associated with Ang II-induced TAA. Smooth muscle cells (SMCs) isolated from adult murine thoracic aorta exhibited excessive mitochondrial fission, oxidative stress, and hyperproliferation in response to Ang II. Treatment with Ang 1-7 resulted in inhibition of mitochondrial fragmentation, ROS generation, and hyperproliferation. Gene expression profiling used for characterization of the contractile and synthetic phenotypes of thoracic aortic SMCs revealed preservation of the contractile phenotype with Ang 1-7 treatment. In conclusion, Ang 1-7 prevented Ang II-induced vascular remodeling and the development of TAA. Enhancing Ang 1-7 actions may provide a novel therapeutic strategy to prevent or delay the progression of TAA.