**3. Classification**

*New Insight into Cerebrovascular Diseases - An Updated Comprehensive Review*

increased calcification in vascular tissue with an unknown mechanism. This effect

Vascular smooth muscle cells (VSMCs) play an important role in the pathology of vascular calcifications. Vascular smooth muscle cells are of mesenchymal origin. These cells may turn into osteoblasts and chondrocytes under stress. Osteoblast-like cells that contain hydroxyapatite crystals appear in the extracellular matrix during vascular smooth muscle calcification. Subsequently, the number of osteochondrogenic cells increases, and calcification inhibitors are suppressed; an increased regulation of bone mineralization regulating genes and the release of calcified membrane-dependent carriers from smooth muscle cells in these calcifications are observed. In addition, intracellular phosphate concentration increases in osteoblastlike cells due to developing hyperphosphatemia in chronic renal failure. Apoptosis in smooth muscle cells, oxidative stress, remodeling in extracellular matrix, and high levels of metalloproteinases increase vascular calcification, resulting in endo-

Vascular smooth muscle cells are the predominant cell type in the arterial wall. VSMCs are mainly composed of the medial layer of the blood vessels, which are subjected to mechanical stress and pressure of blood flow, and maintain vascular tone and resistance [10]. Calcium functions as a stimulator, and under physiological conditions, intracellular calcium is present in VSCMs to regulate many biophysical and biochemical processes [11]. Although the agents responsible for production of vasospasm have not yet been clearly identified, recently the molecular mechanisms involved in the development of vasospasm mainly based on experimental data in canine two-hemorrhage model are reviewed. The blood products after subarachnoid hemorrhage most likely stimulate many cell membrane receptors to activate the tyrosine kinase pathway of WSCMs. The activation of the tyrosine kinase pathway is associated with continuous elevation of intracellular Ca++ levels and activation of mu-calpain. The increased intracellular Ca++ concentration stimulates Ca++/calmodulin and depends on myosin light-chain kinase to phosphorylate myosin light-chain continuously during vasospasms [12]. Cerebral vasospasm is the most frequent and troublesome complication after aneurysmal subarachnoid hemorrhage. Cerebral vasospasm is considered a treatable clinicopathological entity; it is still responsible for many deaths and serious disabilities among patients suffering

is defined as the statin paradox [8].

*The causes of vascular calcification.*

**Causes of vascular calcification**

• Familial hypercholesterolemia

• Atherosclerosis • Chronic renal failure

• Diabetes mellitus • Hypertension • Smoking • Male gender • Older age

**Table 1.**

**2. Pathophysiology**

thelial dysfunction [9].

from intracranial aneurysm rupture [13].

**46**

Vascular calcifications are divided into two subtypes (**Figure 1**). These are called intima and media calcifications according to the localization of calcification.

Intimal calcifications or the so-called atherosclerotic calcifications begin to occur in the presence of chronic inflammations and/or lipid accumulations. Lipidloaded calcifications in the intima cause intimal thickening and subsequent narrowing of the lumen diameter.

Medial calcifications are characterized by concentric calcium deposits in the tunica media layer. Here, elastin lamellae occur between the smooth muscle cells and the elastin fibers. Medial calcifications cause loss of elasticity in the arteries, resulting in arterial stiffness [9].

#### **Figure 1.**

*The classification of vascular calcification.*
