Smooth muscle-specific deletion of cellular communication network factor 2 causes severe aorta malformation and atherosclerosis.

Aims: Cellular communication network factor 2 (CCN2) is a matricellular protein implicated in fibrotic diseases, with ongoing clinical trials evaluating anti-CCN2-based therapies. By uncovering CCN2 as abundantly expressed in non-diseased artery tissue, this study aimed to investigate the hypothesis that CCN2 plays a pivotal role in maintaining smooth muscle cell (SMC) phenotype and protection against atherosclerosis.

Methods And Results: Global- and SMC-specific Ccn2 knockout mouse models were employed to demonstrate that Ccn2 deficiency leads to SMC de-differentiation, medial thickening, and aorta elongation under normolipidaemic conditions.

MFAP4-Deficiency Aggravates Age-Induced Changes in Resistance Artery Structure, While Ameliorating Hypertension.

Background: Abnormalities of resistance arteries may play essential roles in the pathophysiology of aging and hypertension. Deficiency of the vascular extracellular matrix protein MFAP4 (microfibrillar-associated protein 4) has previously been observed as protective against aberrant arterial remodeling. We hypothesized that MFAP4-deficiency would reduce age- and hypertension-dependent arterial changes in extracellular matrix composition and stiffening.

The angiotensin AT-receptor agonist compound 21 is an antagonist for the thromboxane TP-receptor - Implications for preclinical studies and future clinical use.

Since the AT-receptor (ATR) agonist C21 has structural similarity to the AT-receptor antagonists Irbesartan and Losartan, which are antagonists not only at the ATR, but also at thromboxane TP-receptors, we tested the hypothesis that C21 has TP-receptor antagonistic properties as well. Isolated mouse mesenteric arteries from C57BL/6 J and ATR-knockout mice (ATR) were mounted in wire myographs, contracted with either phenylephrine or the thromboxane A (TXA) analogue U46619, and the relaxing effect of C21 (0.1 nM - 10 µM) was investigated.

Artificial intelligence assisted compositional analyses of human abdominal aortic aneurysms .

Quantification of histological information from excised human abdominal aortic aneurysm (AAA) specimens may provide essential information on the degree of infiltration of inflammatory cells in different regions of the AAA. Such information will support mechanistic insight in AAA pathology and can be linked to clinical measures for further development of AAA treatment regimens. We hypothesize that artificial intelligence can support high throughput analyses of histological sections of excised human AAA.

Nitric oxide (NO) synthase but not NO, HNO or H O mediates endothelium-dependent relaxation of resistance arteries from patients with cardiovascular disease.

Background And Purpose: Superoxide anions can reduce the bioavailability and actions of endothelium-derived NO. In human resistance-sized arteries, endothelium-dependent vasodilatation can be mediated by H O instead of NO. Here, we tested the hypothesis that in resistance arteries from patients with cardiovascular disease, endothelium-dependent vasodilatation is mediated by a reactive oxygen species and not impaired by oxidative stress.