Role of adventitia in vascular remodeling in hypertension: a trophobiological view

The vascular wall has the capacity to undergo remodeling in response to long-term changes or injuries. This is a process of structural rearrangement that involves cell growth, cell death, cell migration, cell modulation and secretion/degradation of extracellular matrix molecules. Vascular remodeling is an adaptive phenomenon, e.g. Glagov's compensatory enlargement in atherosclerosis, but it may grow into vascular diseases, such as hypertension, atherosclerosis, and coronary restenosis after angioplasty. Nowadays paradigms defining the cell biology of vascular diseases are the following: (i) the hypertensive vessel is characterized by hyperinnervation-associated medial thickening due to smooth muscle cell (SMC) hypertrophy/hyperplasia and increased extracellular matrix content, (ii) the atherosclerotic plaque is characterized by SMC/immune cells/increased extracellular matrix-containing intimal thickening, and (iii) the restenotic coronary artery is characterized by SMC/immune cells-containing neointimal thickening. The spontaneously hypertensive rats (SHR), the stroke-prone SHR (SHRSP), the genetically hypertensive (GH) rats, and other genetically hypertensive strains are widely used as a model of human essential hypertension. In this volume of Biomedical Reviews, Bell updates the knowledge about vascular wall neurotrophobiology in relation to the pathogenesis of hypertension in SHR and GH rats. Also, Kondo et al systematize the perivascular nerve-related SMC structural changes in the development of hypertension in SHR and SHRSP. The data presented in these reviews are evaluated mainly in terms of Levi-Montalcini's neurotrophic theory.Biomedical Reviews 1996; 6: 5-10

Nerve-mast cell-nerve growth factor link: the mast cell as yin-yang modulator in inflammation and fibrosis

Inflammation and fibroproliferation are biological responses aiming at recovering from injury. Wound healing is considered a paradigm of such a homeostatic phenomenon. However, what begins as a protective response, in excess becomes a damaging process we call chronic inflammatory-fibroproliferative disease.Biomedical Reviews 1995; 4: 1-6

Born on 19 November 1912: he, George Palade, a man who contributed so much to the progress of modern cell biology

In his 1971 paper George Palade wrote for Albert Claude, the founder of biological electron microscopic method: “Seldom has a field owed so much to a single man”. Herein, we articulate the same words for George Palade, the Teacher of many generations in cell biology research and education. Herein we focus on the paradigm shifts in the cell biology, namely the transition from light to transmission electron microscopy in studying cell protein secretion made by George Palade. Onward, we discuss on the transition from contractile to secretory phenotype of vascular smooth muscle cells initiated by Maria Daria Haust and developed by our research group. Taken together, we argue that one of the present challenges in cell biology is to cultivate secretocentric thinking and thus further focusing on how we could make secretory pathways work for the benefit of human’s health

Adipobiology of inflammation

Besides its importance for glucose, lipid and energy metabolism, the present paradigm defines adipose tissue as thebody's largest endocrine and paracrine organ. Accumulating evidence demonstrates that adipose tissue cells synthesize and release a large number of signaling proteins collectively termed adipokines. Adipokines regulate a broad spectrum of biological processes, with inflammation being a key example. This defines a new field of study: adipobiology of inflammation. Herewe shalldance round it, supposing that the pathogenesis of inflammation-related diseases such as atherosclerosis, thyroid-associated ophthalmopathy, inflammatory bowel diseases, and breast cancer may be influenced by competing stimulatory and inhibitory effects mediated by adipokines. This concept may reveal new tools for the development of adipopharmacology of inflammatory disease.Biomedical Reviews 2005; 16: 83-88

Adipoparacrinology: periprostatic adipose tissue as an example

The global epidemic of obesity (globesity) and related cardiometabolic and cancer diseases has focused attention on adipose tissue biology and the role played by adipose-secreted bioactive molecules (adipokines, neurotrophic factors, fatty acids, prostaglandins, steroid hormones, vitamin D3, NO, H2S) in the regulation of a wide array of physiological and pathological processes. Until recently, physicians have looked upon obesity as an accumulation of external adipose tissue (subcutaneous and abdominal). This was routinely evaluated by anthropometric measurements including body mass index and waist, hip and, recently, neck circumference. However, recent data using non-invasive imaging methods (echography, computed tomography, magnetic resonance imaging, and positron emission tomography), reveal a novel picture of adipotopography (fat mapping). Together with secretory functions, such a topography has been conceptualized as two major subfields of adipobiology, adipoendocrinology and adipoparacrinology. Here we introduce periprostatic adipose tissue as an example of adipoparacrinology of prostate cancer; its implication in the therapy is also outlined.Adipobiology 2011; 3: 61-65

Neural-immune-effector (NIE) cross-talk in vascular trophobiology: proposal for new and not yet exploited purinergic regulatory mechanisms

In a state-of-the-art approach, Dr. Hasséssian presents purinoceptor-mediated vasoconstriction/vasodilation mechanisms of the pulmonary circulation. He focuses on P2 purinoceptors of smooth muscle cells, endothelial cells, platelets and mast cells, without addressing P1 (adenosine) purinoceptors. Recently, the Burnstock's purinoceptorology is "arborizing" into a variety of members of P1 and P2 purinoceptor families classified by the International Union of Pharmacology. Here we would like to add some possible, new and not yet exploited, purinergic regulatory mechanisms to the Hasséssian's work. Accordingly, we shall briefly focus on the involvement of connective tissue (adventitial) mast cells and their interactions with perivascular nerves and medial smooth muscle cells.Biomedical Reviews 1994; 3: 81-86

A suggestive neurotrophic potential of mast cells in heart and submandibular glands of the rat

According to the neurotrophic theory, the nerve growth factor (NGF) is widely distributed in the effector tissues of peripheral sympathetic and sensory neurons, suggesting that the density of innervation is controlled by effector derived NGF. Sympathetic neurons require access to NGF for survival throughout life, whereas sensory neurons are dependent on NGF only during restricted period of embryonic development. This development-related feature of sympathetic neurons suggests that they crucially depend on plasticity of NGF biology, including secretion, availability, and utilization, to maintain appropriate neuronal function in adult life, and even in old age. While most previous studies on the cellular source of NGF have focused on neuronal and nonneuronal effector cells, it was recently demonstrated that NGF secretion is not only restricted to cells receiving a direct innervation. Immune cells, including mast cells (MC), lymphocytes and macrophages, for example, produce and release NGF as well as NGF secretion-inducing cytokines. Likewise, since the first evidence that NGF treatment causes a significant increase in the number and size of MC has been published by Aloe and Levi-Montalcini in 1977, it has been repeatedly shown that these cells are also NGF-responsive cells, thus providing further evidence for a widely investigated MC-nerve interaction. Further on this trophobiological line, a positive correlation of the amount of NGF and expression of NGF mRNA with the density of sympathetic innervation was demonstrated in a variety of organs. In the rat heart, one such example, the atrium contains a higher amount of NGF corresponding to a denser sympathetic nerve supply compared to the ventricle. Such a correlation was also revealed in the submandibular glands (SMG) and iris. Likewise, the density of MC in the ankle joint capsule, which is heavily innervated, is greater than in the capsule of the knee, which is less densely innervated, and the MC number in the synovial joint of spontaneously hypertensive rats, which have increased sympathetic nerve supply, is significantly greater than in normotensive rats. A summing-up of the above mentioned data shows that (i) MC are NGF secreting/responsive cells and frequently colocalized with nerves, and (ii) a higher NGF amount correlates with a denser sympathetic innervation of a tissue . This, in our eyes, brings into question the sole contribution of the "classical" effector cells to neurotrophic support of sympathetic nerve-innervated tissues. Consequently, we suggest that MC, through their own and/or cytokine-induced NGF secretion, may also be implicated in the neurotrophic potential in these tissues.Biomedical Reviews 1998; 9: 143-145

Neuroimmune hypothesis of atherosclerosis

Although "many roads lead to atheroma", the prevailing hypothesis at present is the Russell Ross` response-to-injury hypothesis, which states that atherosclerosis is an inflammatory disease that involves several aspects of wound healing. It is noteworthy that, emphasized by the current studies of neurotrophic factors and nerve-immune cell interactions, neuroimmune mechanisms are increasingly implicated in the pathogenesis of a number of inflammatory diseases. Here we highlight the possibility that neuroimmune mechanisms, including the participation of neurotrophic factors and immune cells, may also be involved in the process of atherogenesis.Biomedical Reviews 1999; 10: 37-44

Homage to George E. Palade Cell Protein Secretion in Vascular Biology: Overview and Updates

Abstract This short overview and updates expresses our brain-and-heart homage to George Emil Palade, "the most influential cell biologist ever". In his 1971 paper Palade wrote for Albert Claude, the founder of biological electron microscopic method: "Seldom has a field owed so much to a single man". Herein, we articulate the same words for George Palade, the Teacher of many generations in cell biology research and education. Accordingly, we focus on two paradigm shifts in the cell biology, namely (i) the transition from light to transmission electron microscopy in studying cell protein secretion made by George Palade, and (ii) the transition from contractile to secretory phenotype of vascular smooth muscle cells made by Maria Daria Haust followed and developed by our research group. Altogether, we argue that one of the present challenges in vascular biology is to cultivate secreto-centric thinking and thus further focusing on how we could make the vascular muscle's secretory pathways work for the benefit of human's cardiovascular health

State-of-the-artery: periadventitial adipose tissue (tunica adiposa)

Traditional view considers that the arterial wall is composed of three concentric tissue coats (tunicae): intima, media, and adventitia. However, large- and medium-sized arteries, where usually atherosclerosis develops, are consistently surrounded by periadventitial adipose tissue (PAAT). Here we update growing information about PAAT, and  conceptualize it as the fourth coat of arterial wall, that is, tunica adiposa (in brief, adiposa, like intima, media, adventitia). Recent evidence has revealed that adipose tissue expresses not only metabolic, but also secretory (endo- and paracrine) phenotype, producing/releasing a large number of signaling proteins collectively termed adipokines. Through paracrine ("vasocrine") way, adiposa-derived mediators may contribute to various arterial functions such as contraction-relaxation, smooth muscle cell growth, inflammation, hemostasis, and innervation, hence to "outside-in" signaling pathway of atherogenesis.Biomedical Reviews 2009; 20: 41-44