Future perspectives and concluding remarks

Apparently there are numerous factors influencing the outcome in attempts to define the vascular transcriptome. In addition to exploring normal endothelium, there is also the task of defining transcriptomes of ECs in pathological conditions, such as in various forms of cancer, retinopathies, and diabetic complications. Both Seaman et al.⁸¹ and Herbert et al.⁸² made clever efforts in finding endothelial markers in solid tumors, and these kinds of experiments will probably be more extensively explored in the future.

Another common family of pathologies involving ECs is arteriosclerosis, i.e. hardening and thickening of the arterial vessel wall as a result of macrophages infiltration, formation of lipid/cholesterol plaques, calcification, or other factors (reviewed in¹⁰⁶). In addition to reduced lumen diameter, another characteristic of arteriosclerosis is endothelial dysfunction (reviewed in¹⁰⁶) where ECs fail to synthesize sufficient amounts of nitric oxide (NO) leading to decreased vasodilatory ability. In addition to the other pathologies mentioned, the several different states and conditions in the

arteriosclerosis family of disease would be of great interest to define using transcriptional profiling on human samples.

To obtain the most comprehensive view on the vascular transcriptome, it is probably beneficial to combine all available datasets containing profiles on various ECs regardless of their origin, e.g. despite differences in species, endothelial subset, technical platform, or other variables, rather than excluding certain data sets. As it is almost impossible to expect only one or a few expression profiling experiments to reveal the full vascular transcriptome, a more inclusive approach would likely be most profitable. This type of meta-analysis of all endothelial-related transcriptional data in the public domain would require a substantial effort, but would likely provide a more comprehensive and accurate dataset. Our current understanding of the vascular transcriptome, both as a way of looking at thousands of genes at the same time as looking at individual genes involved in essential pathways, may be illustrated as a jigsaw puzzle in the process of being completed (Figure 9).

Figure 9. The vascular puzzle.

Further addition of other –omics types of data, such as proteomics and interactomics, could be imagined as an increase in the number of dimensions of the puzzle. Perhaps the final puzzle, containing all kinds of vascular data, would have far more dimensions than the three we can perceive.

The discoveries made in Papers I-II on individual genes and the angiogenesis-related pathways they are crucially involved in, are contributions to some aspects of the puzzle.

Papers III-IV rather contributes with sets of genes important in vascular biology, thereby putting additional pieces of the puzzle together. However, regardless of how many pieces of the puzzle that will be correctly put together, there will probably always be missing, or mismatching, pieces. As annoying as this might be, these pieces are the constituents of the source of curiosity that will allow us all to keep continuing asking questions, and to ensure that there are always new discoveries to be made.

8 ACKNOWLEDGEMENTS

I would like to express my deepest gratitude to everyone who in numerous different ways helped me put this thesis together; you are all such great teachers! I would especially like to acknowledge the following:

Christer Betsholtz, my supervisor and coach, multi-tasking magician and circus director, for sharing your enthusiasm, fighting spirit, and creating such an excellent scientific environment. Without your everlasting support, encouragement, and faith in me, I would not be the person I am today.

Mats Hellström, my co-supervisor, bilhandlare, mentor, and friend, for all the fantastic discussions, data-interpretation-marathons, and highly appreciated espresso breaks. With your sparkling intellect and great sense of humor, you really taught me how to do research.

Mattias Kalén, my dear friend, and great thinker, for all the interesting discussions ranging from life in general to detailed matters of science, your fearless and explorative way of living, and the laughs that could brighten any day.

Simin Rymo, my darling friend, for amazing support, all the great talks with so much depth and humor, teaching me how to live the life I want, your strength, and wonderful friendship.

Ying Sun, my great friend, for all the lovely chats, your great sense of humor, and always being brave.

The current members of the Betsholtz team: Maya Nisancioglu, for the enjoyable (and sometimes a bit too adventurous...), trips around the world, and help to create a comfortable work environment. Liqun He, my teacher in bioinformatics, for all the interesting discussions, and always helping me with great patience.

Guillem Genové, for exciting discussions, for highlighting the importance of bulle, and bringing a Mediterranean flavor to the lab. Karin Strittmatter, for nice chats, and always helping me with the weirdest little things. Konstantin Gaengel, for always being interested in discussing science, and sharing your kindness. Johanna Andrae, wild life expert, for always lending a helping hand when needed, and your good mood. Annika Armulik, for intellectual discussions, and introducing me to the Estonian riviera. Kazuhiro Hagikura, for your knowledge on Japanese brands of whiskey and their origins, and your nice way of being.

Jenny Norlin, for being a fellow old-school microarrayer. Radiosa Galini, for bringing an Italian vibe to the lab. Sara Kamph, for always having a minute to talk. Long Long, for your enthusiasm.

The following former members of the Betsholtz group: Holger Gerhardt, my friend, for your continuous support, many laughs, and your positive outlook on life and people. Minoru Takemoto, for the great development of the Microarray Factory, and creation of an intellectual yet friendly atmosphere. Desiree von Tell, for nice dinners, and your excellent interior design skills. Cecilia Bondjers, for taking isolation of microvasculature to a higher level. Alexandra Abrahamsson, for inventing the best IHC protocols. Johan Dixelius, for bringing tasty fruit to the lab. Maria Enge and Mattias Bjarnegård, for helping me out when being new at almost everything.

Karl Tryggvason and the members of his group, for creating a good scientific environment in the Matrix Biology division, both in the labs and in the lunch room. Ann-Charlotte Andersson, Ann-Sofie Nilsson, Anna Domogatskaya, Anne-May Österholm, for nice chats, Asmundur Oddsson, Berit Rydlander, Bing He, Dadi Niu, for always being friendly, Elisabeth Raschperger, Elisabeth Åman, Eyrun Hjorleifsdottir, Gunvor Alvelius, Jaakko Patrakka, Juha Ojala, Kan Katayama, Ljubica Perisic, Mark Lal, Masatoshi Nukui, for your sense of humor, Sergey Rodin, Susan Warner, Timo Pikkarainen, for nice talks, Xiangjun Xu, Yi Sun, and Zhijie Xiao. Kerstin Bengtson, for all the help during my first year.

Former member Stefania Cotta-Done, for your bright smiles, and all your fabulous shoes.

Arindam Majumdar, for exciting discussions, always with a friendly attitude. Lwaki Ebarasi, for your good mood, and enjoyable talks every now and then. Sajila Kisana and Sunil Udumala.

Karin Julenius.

Group Lindahl, including: Per Lindahl, for creatively bringing interdisciplinary science into focus, and being such a nice person. Erik Larsson, for interesting and hilarious discussions regarding genomics, as well as the

habitat and behavior of the bergstunga, your great sense of humor, and crucial help on bioinformatic matters.

Henrik Lindskog, fellow BVLP:are, for friendship, and nice talks. Former member Stefan Scheidl, for being a microarray pioneer, and your efforts in trying to teach me how to waltz.

The former AngioGenetics crew, including: Noomi Asker, my friend and office mate, for all talks, laughs, and your way of making things better. Linda Karlsson, unchallenged queen of ISH, for your lovely sense of humor, and teaching me so many things. Elizabeth Norseng, bioinformatics- and yoga expert, for a lot of fun, and great work. Lisa Athley, for introducing me to Josef-yoga, and the unforgettable trip to Santa Fe.

Tore Samuelsson, for showing me the bioinformatics-world with great patience and friendliness, and being a co-inventor of the most delicious fish stew/soup/bouillabaisse ever made at a company kick-off. Ann-Christin Häger, for always coming to work with a smile. Mattias Karlsson, for nice chit-chats.

The Uffe-squad, including: Ulf Eriksson, my bonus-supervisor, for your energetic and open minded way of approaching any discussion, and introducing me to VEGF-B biology. Carolina Rosenlew, my friend and colleague, for your undeniably positive attitude, all the support during easy and difficult times, and making any conference enjoyable. Monika Ehnman, for the nice talks, and room sharing in Toronto. The Pietras division, including: Kristian Pietras, for fun and creative discussions, and your nice personality. Charlotte Hägnan, BJJ queen, for great company, and your good mood.

The group of Kari Alitalo, especially Tuåmas Tammela for exciting collaborations, interesting and enjoyable correspondence, and showing me what a perfect thesis should look like.

Jeffrey Essner, for fun and interesting collaborations, and your grand fishing expertise.

Bo Olsson, my former high-school science teacher, for always believing in me.

Helena Ohlsson, darling friend and former BVLP:are, for great friendship, your fantastic sense of humor, for always being there, and since you always know the answer to “Hur vet man att man är i Götteborrg?”.

Erik Norvell, my friend, for all the laughs, and talks about everything.

Daniel Liothe, for friendship, training, and philosophy. Tina Liothe, for friendship, and shared affection for Saltholmen. Fredrik Simu, for being who you are.

My darling gang of Muppet friends that makes my life so much brighter: Caroline Améen, fitness queen, for great friendship, numerous Zenit breakfasts with Sandra, the absolutely craziest trip to London ever known to mankind, and shared påskäggsfrosseri,. Sandra Rodrigo Blomqvist, martial arts- and cocktail expert, for great friendship, your and Caroline’s many visits to Stockholm that cheered me up immensely, shopping Glasgow to bits, and all the nice talks. Kajsa Améen, teaching master, for joint jumping into jacuzzis with surprisingly few bubbles, your wonderful laughter, and being the world champion in the nynnatävling. Ulla and Torkel Améen, for all the enjoyable stays in Hunnebostrand.

Cathrine Waldenvik, for the great friendship that goes back so far, endless summer nights at the balcony of my parent’s house, introducing me to the Sundays and all the wonderful music that followed, sharing of the darker moments, and teaching me how to live a true life.

All the fantastic yoga teachers, especially Örjan Abrahamsson and Sabina Derneby, for guidance in the art of breathing, and helping me bring back the light within. Ashtanga-Camilla, for showing me how to re-discover the bliss of ashtanga yoga. Om shanti, my friends.

Carola Fredstrand, fellow yogini and dear friend, for lovely tea moments after classes, helping me unravel the mysteries of life and relationships, and being so generous.

Susanne Schwalbe, for you warm and friendly nature, and being such an excellent training companion.

Åsa Wallentin, friend and sister-in-law, for introducing me to the magnificent, fluffy, hero Canis, and being such a nice person.

My dear family, for love and endless support: Mamma Kerstin, for all the fun shopping sprees, and making the best food in the world. Pappa Gunnar, for always believing that I can do anything I set my mind to. My sister Monika, for backing me up no matter what, all the fun things we have done, and loving care. My sister Annika, for always having a positive attitude. Juliana, for never giving up. My brother Jerker, for fun hikes in the woods of Småland. Gunilla and Erik, for happy reunions in Huskvarna.

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