## 1 Introduction  
The most frequent risk factor for myocardial infarction, congestive heart failure, and stroke is hypertension [1; 2]. Nifedipine is used as an antihypertensive and antianginal agent, providing vascular smooth muscle relaxation and negative ionotropic and chronotropic effects on. This drug is able to inhibit voltage-dependent L-type calcium channels in vascular smooth muscles and myocardial cells, preventing the entry of calcium ions. The reduction of intracellular calcium level causes a decrease of peripheral arterial vascular resistance and the dilatation of coronary arteries. These conditions result in systemic blood pressure reduction and in myocardial oxygen delivery increase [3; 4; 5; 6]. The systematic review and meta-analysis by [PERSON] et al. [7] analyzed the side effects of antihypertensive agents on 28,922 patients, reporting that calcium channel blockers are most associated with neurologic (17.6%), cardiovascular (11.9%), respiratory (7.8%), and dermatologic (6.8%) adverse events. The literature also proved gingival overgrowth (GO) to be a further side effect associated with the administration of calcium channel blockers,including nifedipine. The cross-sectional study by [PERSON] et al. [8] recorded a significantly higher prevalence of gingival enlargement in 65 patients treated with nifedipine compared with the control group, and it also assessed, in line with other studies, that gingival lesions were more severe in the vestibular area of inferior and anterior teeth [9; 10].  
The onset of gingival overgrowth is not only associated with antihypertensive therapy, but also with anticonvulsant and immunosuppressived drugs' chronic administration: the prevalence of drug-induced gingival enlargement (DIGO) was demonstrated to be around 50-70%, 30%, and 25-30% in the case of phenytoin [11; 12], nifedipine [8], and cyclosporine, respectively [12]. Clinical manifestation of GO is similar for all the cited drugs: it usually manifests itself during the first 3 months of the therapy, reaching its widest expression after 9-12 months [13]. The study of 2012 by [PERSON] et al. [14] described the manifestation of gingival lesions, evaluating two clinical indices, i.e., vertical and horizontal overgrowth: GO occurs at first in the area of interdental papilla, as localized nodullary enlargement (horizontal growth), and it afterwards expands to the dental crown (vertical growth), interfering with mastication. The severity of drug-induced gingival enlargement (DIGO) seems to be influenced by plaque scores and gingival inflammation [15]. In particular, with reference to nifedipine, some studies demonstrated that the onset and the development of GO depends on high plaque index, administration of high drug doses, and genetic factors [16; 17]. Moreover, [PERSON] et al. assessed that the characteristics of GO induced by nifedipine, phenytoin, and ciclosporin are different: gingival lesions associated with anticonvulsants are the most fibrotic, gingival tissue in patients treated with cyclospor appears highly inflamed, while lesions related to nifedipine administration have intermediate characteristics [18].  
The increase of the volume of gingival tissues represents the consequence of the connective tissue response: the alterations in cellular and extracellular matrix (ECM) metabolisms leads to an excessive storage of extracellular matrix proteins (collagens or amorphous ground substance) [15; 19]. Calcium channel blockers can inhibit the intracellular calcium uptake, an event that leads to the stimulation of gingival fibroblasts, which are mainly involved in the synthesis and enzymatic degradation of ECM proteins. The pathogenetic hypothesis of DIGO is based on the presence of genetically predisposed gingival fibroblasts, which produce enormous quantity of collagen, consequently causing a disproportion in the collagen synthesis-degradation mechanism [13; 20]. Some authors demonstrated otherwise that the storage of collagen in DIGO is the result of the inhibition of the collagen degradation process [21].