Peripheral arterial disease can involve tissue loss in up to 50% of patients with diabetic foot syndrome (DFS). Consequently, revascularization of narrowed or occluded arteries is one of the most common forms of comprehensive treatment. However, technically successful angioplasty does not always result in the healing of ulcers. The pathomechanism of this phenomenon is still not fully understood, but inadequate angiogenesis in tissue repair may play an essential role. Changes in pro- and anti-angiogenic factors among patients with DFS are not always clear and conclusive. In particular, some studies underline the role of decreased concentration of pro-angiogenic factors and higher levels of anti-angiogenic mediators. Nevertheless, there are still controversial issues, including the paradox of impaired wound healing despite high concentrations of some pro-angiogenic factors, dynamics of their expression during the healing process, and their mutual relationships. Exploring this process among diabetic patients may provide new insight into well-known methods of treatment and show their real benefits and chances for improving outcomes.

Due to the fact that cardiovascular diseases (CVDs) have become the most serious problem in public health, there is a need for new and efficient methods for screening and early detection. In the recent literature, saliva and gingival crevicular fluid (GCF) have been gaining recognition as sources of many potential biomarkers of various systemic diseases, mainly because of correlation between the level of some compounds in the blood and saliva and association between the composition of saliva and health status. In this review, we summarize published findings of patients with atherosclerosis, arterial hypertension, coronary artery disease (CAD), acute coronary syndrome (ACS), and stroke in the context of clinical utility of saliva and GCF in diagnosing and assessing CVD severity. We hypothesize that substances in saliva including inflammatory markers, enzymes, or hormones might become novel contributors to the diagnosis and screening of CVDs. In particular, C-reactive protein (CRP), tumor necrosis alpha (TNFα), and cortisol seem to be the most promising. However, further investigation is warranted to determine the most effective markers and methods for their analysis.

Blood-flow-restricted exercise (BFRE) has been gaining constantly increasing interest in rehabilitation, but its influence on endothelial functions has not been well studied yet. Our aim is to examine the influence of low-resistance BFRE on endothelial functions and angiogenesis. This prospective cross-over study involved 35 young healthy adults. They conducted a 21-min low-resistant exercise with blood flow restricted by pressure cuffs placed on arms and tights. They also did the same training but without blood flow restriction. Endothelial parameters and angiogenesis biomarkers were evaluated before and up to 20 min after exercise. Both types of exercise increased Flow-Mediated Dilatation (FMD) but elevation after BFRE was more significant compared to the controls. The stiffness index decreased only after BFRE, while the reflection index decreased significantly after both types of exercise but was higher after BFRE. Platelet endothelial cell adhesion molecule (PECAM-1) and vascular endothelial growth factor receptor 2 (VEGFR-2) concentrations were increased by both exercise types but elevations were higher after BFRE compared to the controls. Only BFRE elevated the mean serum CD34 protein concentration. Based on these results, we can assume that low-resistance BFR exercise stimulates angiogenesis and improves endothelial functions more significantly compared to the same training performed without blood flow restriction.

Peripheral arterial disease (PAD)-induced ischemia is an important component of diabetic foot syndrome (DFS). The results of revascularization of the lower extremity arteries (including percutaneous transluminal angioplasty [PTA]) do not always give satisfactory long-term results, which is due to many factors. The aim of the study was to investigate the alterations in selected circulating angiogenic factors and microcirculation parameters in 41 patients with DFS following PTA and analyze their relationships with clinical outcomes during 1-year follow-up. Our study revealed a general decrease in pro-angiogenic factor levels after PTA and their subsequent stabilization during subsequent observation. The results indicated a significant association between plasma circulating FGF-2 level and poor outcomes (including the incidence of restenosis/reocclusion of treated arteries) during 12 months of observation. The perioperative changes in FGF-2 showed a significant association with LDF alterations after PTA. Follow-up 1–3 months post-intervention showed a tendency towards elevated TcpO2, VEGF-A, and VEGF-R2 levels in patients free from adverse events. These results may provide a basis for further research on the potential use of selected circulating angiogenic factors for monitoring the treatment of patients with DFS following PTA.

Despite clear evidence of inadequate angiogenesis in ischemic diabetic foot syndrome (DFS) pathogenesis, angiogenic factor level changes in patients with ischemic DFS remain inconsistent. This study aimed to assess circulating angiogenic factors concerning ischemic DFS advancement and describe their relationships with patients’ clinical characteristics, microvascular parameters, and diabetic control. The study included 41 patients with ischemic DFS (67.3 (8.84) years; 82.9% males). Angiogenic processes were assessed by identifying circulating concentrations of five pro- and two anti-angiogenic factors. We found that penetrating ulcers were related to a significantly higher FGF-2 level (8.86 (5.29) vs. 5.23 (4.17) pg/mL, p = 0.02). Moreover, plasma FGF-2 showed a significant correlation with the SINBAD score (r = 0.32, p = 0.04), platelet count (r = 0.43, p < 0.01), white cell count (r = 0.42, p < 0.01), and age (r = −0.35, p = 0.03). We did not observe any significant linear relationship between the studied biomarkers and microcirculatory parameters, nor for glycemic control. In a univariate analysis using logistic regression, an increase in plasma FGF-2 was tied to greater odds of high-grade ulcers (OR 1.16; 95% CI 1.02–1.38, p = 0.043). This suggests that circulating FGF-2 may serve as a potential biomarker for predicting DFU advancement and progression. It is necessary to conduct further studies with follow-up observations to confirm this hypothesis.