Fabio Fimiani

Inflammation and Cardiovascular Disease: From Pathogenesis to Therapeutic Target

Atherosclerosis represents the most common pathological substrate of coronary heart disease (CHD), and the characterization of the disease as a chronic low-grade inflammatory condition is now largely accepted. A number of mediators of inflammation have been widely studied, both as surrogate biomarkers and as causal agents, in the pathophysiological network of atherogenesis and plaque vulnerability. The epidemiological observation that biomarkers of inflammation are associated with clinical cardiovascular risk supports the theory that targeted anti-inflammatory treatment appears to be a promising strategy in reducing residual cardiovascular risk on the background of traditional medical therapy. A large number of randomized controlled trials have shown that drugs commonly used in cardiovascular disease (CVD), such as statins, may be effective in the primary and secondary prevention of cardiovascular events through an anti-inflammatory effect. Moreover, several anti-inflammatory drugs are being tested for their potential to reduce residual cardiovascular risk on the background of validated medical therapy for atherosclerotic disease. In this paper, we review relevant evidence with regard to the relationship between inflammation and CVD, from pathogenesis to therapeutic strategies.

The Role of von Willebrand Factor in Vascular Inflammation: From Pathogenesis to Targeted Therapy

Beyond its role in hemostasis, von Willebrand factor (VWF) is an emerging mediator of vascular inflammation. Recent studies highlight the involvement of VWF and its regulator, ADAMTS13, in mechanisms that underlie vascular inflammation and immunothrombosis, like leukocyte rolling, adhesion, and extravasation; vascular permeability; ischemia/reperfusion injury; complements activation; and NETosis. The VWF/ADAMTS13 axis is implicated in the pathogenesis of atherosclerosis, promoting plaque formation and inflammation through macrophage and neutrophil recruitment in inflamed lesions. Moreover, VWF and ADAMTS13 have been recently proposed as prognostic biomarkers in cardiovascular, metabolic, and inflammatory diseases, such as diabetes, stroke, myocardial infarction, and sepsis. All these features make VWF an attractive therapeutic target in thromboinflammation. Several lines of research have recently investigated “tailor-made” inhibitors of VWF. Results from animal models and clinical studies support the potent anti-inflammatory and antithrombotic effect of VWF antagonism, providing reassuring data on its safety profile. This review describes the role of VWF in vascular inflammation “from bench to bedside” and provides an updated overview of the drugs that can directly interfere with the VWF/ADAMTS13 axis.

Can apical ballooning cardiomyopathy and anterior STEMI be differentiated based on β1 and β2-adrenergic receptors polymorphisms?

AIM Catecholamine excess along with an exaggerated sympathetic stimulation appears to play a major role in the pathophysiological mechanism of tako-tsubo cardiomyopathy (TTC), which mimics acute ST-elevation myocardial infarction (STEMI). The aim of the present study was to investigate differences in the distribution of allelic variants of β1- and β2-adrenoceptors between TTC and anterior STEMI patients compared to normal subjects. METHODS AND RESULTS β1- and/or β2-adrenoceptor polymorphisms in 97 patients with TTC (92 females, 96%; mean age 66.8±11.6years; range 35 to 87years) were compared with 81 patients with anterior STEMI (77 females, 95%; mean age 72.5±12.8years; range 32 to 96years) and 101 controls (95 females, 94%; mean age 62.3±10.4years; range 44 to 92years). Differences in genotype frequencies were assessed using the Pearson χ(2) test. β1-Adrenoceptor (Gly389Arg) and β2-adrenoceptor (Arg16Gly and Gln27Glu) genotype frequencies were significantly different among groups (p<0.001, p=0.024, p=0.008, respectively). However, differences did not achieve statistical significance when TTC and anterior STEMI patients were compared by post-hoc analysis. The cardiovascular risk factor profile was worse in anterior STEMI patients, who more often had a history of systemic arterial hypertension, diabetes and coronary artery disease. CONCLUSIONS In a large TTC cohort compared with anterior STEMI patients, β-adrenoceptor polymorphisms were similar. However, the cardiovascular risk factor profile was different between the two groups. β-Adrenoceptor polymorphisms in TTC patients differed from normal subjects.

Von Willebrand Factor as a Novel Player in Valvular Heart Disease: From Bench to Valve Replacement

von Willebrand Factor (vWF) is a well-known mediator of hemostasis and vascular inflammation. Its dynamic modulation in the bloodstream, according to hemodynamic conditions, makes it an appealing biomarker in patients with valvular heart disease (VHD). Recent studies highlight the close connection between vWF and VHD, with possible implications in the pathogenesis of VHD, promoting valve aging and calcification or favoring the development of infective endocarditis. Moreover, vWF has been recently proposed as a new diagnostic and prognostic tool in patients with valve stenosis or regurgitation, showing a strict correlation with severity of valve disease, outcome, and bleeding (Heyde syndrome). A novel role for vWF is also emerging in patients undergoing percutaneous or surgical valve repair/replacement to select and stratify patients, evaluate periprocedural bleeding risk, and detect procedural complications. We also report our single-center experience, suggesting, for the first time, possible clinical implications for vWF in percutaneous mitral valve repair (MitraClip). This review summarizes recent advances in the role of vWF in VHD with an updated overview going from bench to operating room.